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Abstract:

Neuromodulation cryotherapeutic devices and associated systems and
methods are disclosed herein. A cryotherapeutic device configured in
accordance with a particular embodiment of the present technology can
include an elongated shaft having distal portion and a supply lumen along
at least a portion of the shaft. The shaft can be configured to locate
the distal portion intravascularly at a treatment site proximate a renal
artery or renal ostium. The supply lumen can be configured to receive a
liquid refrigerant. The cryotherapeutic device can further include a
cooling assembly at the distal portion of the shaft. The cooling assembly
can include an applicator in fluid communication with the supply lumen
and configured to deliver cryotherapeutic cooling to nerves proximate the
target site when the cooling assembly is in a deployed state.

Claims:

1. A cryotherapeutic device, comprising: an elongated shaft with a distal
portion, the shaft being configured to locate the distal portion
intravascularly at a treatment site within or otherwise proximate a renal
artery or renal ostium; a supply lumen along at least a portion of the
shaft, the supply lumen being configured to receive liquid refrigerant;
and a cooling assembly at the distal portion, the cooling assembly having
a delivery state and a deployed state, the cooling assembly including an
orifice and an applicator including a first balloon and a second balloon
the orifice being in fluid communication with the supply lumen, the first
balloon having a heat-transfer portion in fluid communication with the
orifice, wherein the second balloon is at least partially collapsed in
the delivery state, wherein the heat-transfer portion has a heat-transfer
rate in the deployed state while the cooling assembly receives
refrigerant sufficient to cause therapeutically-effective, cryogenic
renal-nerve modulation, and wherein the heat-transfer portion is
non-circumferential at longitudinal segments along the length of the
cooling assembly.

2. A cryotherapeutic device, comprising: an elongated shaft with a distal
portion, the shaft being configured to locate the distal portion
intravascularly at a treatment site within or otherwise proximate a renal
artery or renal ostium; a supply lumen along at least a portion of the
shaft, the supply lumen being configured to receive liquid refrigerant;
and a cooling assembly at the distal portion, the cooling assembly having
a delivery state and a deployed state, the cooling assembly including an
orifice and an applicator including a first balloon and a second balloon,
the orifice being in fluid communication with the supply lumen, the first
balloon having a first heat-transfer portion in fluid communication with
the orifice, the second balloon having a second heat-transfer portion,
and the second balloon being at least partially collapsed in the delivery
state, wherein the first heat-transfer portion is generally less
compliant than the second heat-transfer portion, wherein the first
heat-transfer portion has a first heat-transfer rate in the deployed
state while the cooling assembly receives refrigerant sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation, wherein the
second heat-transfer portion has a second heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant less than
the first heat-transfer rate, and wherein the first heat-transfer portion
is non-circumferential at longitudinal segments along the length of the
cooling assembly.

3. The cryotherapeutic device of claim 2, wherein the first balloon is
less compliant than the second balloon.

4. The cryotherapeutic device of claim 2, wherein the first balloon is
generally non-compliant and the second balloon is generally compliant.

5. The cryotherapeutic device of claim 2, wherein: the first balloon has
a generally D-shaped cross-sectional area, the first heat-transfer
portion is generally non-compliant, the second balloon has a generally
C-shaped cross-sectional area connected to the generally D-shaped
cross-sectional area of the first balloon, and the second heat-transfer
portion is generally compliant.

6. The cryotherapeutic device of claim 2, wherein the applicator is
expandable and configured to completely occlude renal arteries or renal
ostiums having different cross-sectional dimensions.

7. The cryotherapeutic device of claim 2, wherein the second balloon in
the deployed state is configured to thermally insulate a portion of the
treatment site from the first balloon.

8. The cryotherapeutic device of claim 2, wherein the applicator includes
a partition between the first balloon and the second balloon, the
partition being generally non-compliant.

9. The cryotherapeutic device of claim 2, wherein the first balloon
defines a first chamber, the second balloon defines a second chamber, the
first chamber is fluidly separate from the second chamber, the device
further comprises a filler lumen along at least a portion of the shaft,
and the filler lumen is configured to supply filler material to the
second chamber.

10. The cryotherapeutic device of claim 2, wherein-- the cooling assembly
has a first length, the first balloon is elongated and has a second
length, the second balloon is elongated and has a third length, and the
first, second, and third lengths are generally parallel in the deployed
state.

11. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion having a length, the shaft being configured to locate the
distal portion intravascularly at a treatment site within or otherwise
proximate a renal artery or renal ostium; a supply lumen along at least a
portion of the shaft, the supply lumen being configured to receive liquid
refrigerant; and an applicator at the distal portion of the shaft, the
applicator having a delivery state and a deployed state and including a
first chamber and a second chamber, the first chamber having a first
heat-transfer portion in fluid communication with the supply lumen, and
the second chamber having a second heat-transfer portion, wherein the
first heat-transfer portion is generally less compliant than the second
heat-transfer portion, wherein the first heat-transfer portion has a
first heat-transfer rate in the deployed state while the cooling assembly
receives refrigerant sufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation, wherein the second heat-transfer
portion has a second heat-transfer rate in the deployed state while the
cooling assembly receives refrigerant less than the first heat-transfer
rate, and wherein the first heat-transfer portion extends around less
than a full circumference of the applicator in a plane perpendicular to
the length.

12. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion, the shaft being configured to locate the distal portion
intravascularly at a treatment site within or otherwise proximate a renal
artery or renal ostium; a supply lumen along at least a portion of the
shaft, the supply lumen being configured to receive liquid refrigerant; a
cooling assembly at the distal portion of the shaft, the cooling assembly
having a delivery state and a deployed state, the cooling assembly
including an orifice and an applicator including a first balloon and a
second balloon, the orifice being in fluid communication with the supply
lumen, the first balloon defining a first chamber and having a first
heat-transfer portion in fluid communication with the orifice, the second
balloon defining a second chamber and having a second heat-transfer
portion, and the second balloon being at least partially collapsed in the
delivery state, wherein the first heat-transfer portion has a first
heat-transfer rate in the deployed state while the cooling assembly
receives refrigerant sufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation, wherein the second heat-transfer
portion has a second heat-transfer rate in the deployed state while the
cooling assembly receives refrigerant less than the first heat-transfer
rate, and wherein the first heat-transfer portion is non-circumferential
at longitudinal segments along the length of the cooling assembly; a
first exhaust passage along at least a portion of the shaft, the first
exhaust passage being configured to transport refrigerant from the first
chamber; and a second exhaust passage along at least a portion of the
shaft, the second exhaust passage being configured to transport
refrigerant from the second chamber and being fluidly separate from the
first exhaust passage.

13. The cryotherapeutic device of claim 12, further comprising: a first
pressure regulator in fluid connection with the first exhaust passage;
and a second pressure regulator in fluid connection with the second
exhaust passage.

14. The cryotherapeutic device of claim 12, wherein-- the first balloon
has a first internal surface area, the second balloon has a second
internal surface area, the orifice is a first orifice having a first
free-passage area, the first chamber is in fluid communication with the
first orifice, the cooling assembly further comprises a second orifice
having a second free-passage area, the second chamber is in fluid
communication with the second orifice, and a ratio of the first
free-passage area to the first surface area is greater than a ratio of
the second free-passage area to the second surface area.

15. The cryotherapeutic device of claim 12, wherein-- the orifice is a
first orifice, the first chamber is in fluid communication with the first
orifice, the cooling assembly further comprises a second orifice, the
second chamber is in fluid communication with the second orifice, the
first orifice and the first chamber are configured for generally
surface-area limited cooling in the deployed state, and the second
orifice and the second chamber are configured for generally
refrigerant-limited cooling in the deployed state.

16. The cryotherapeutic device of claim 12, wherein the cooling assembly
in the deployed state is configured to circulate refrigerant within the
first chamber at a first average temperature and to circulate refrigerant
within the second chamber at a second average temperature, the first
average temperature being lower than the second average temperature.

17. The cryotherapeutic device of claim 12, wherein the applicator
includes a third balloon, the first and second balloons being within the
third balloon.

18. The cryotherapeutic device of claim 12, wherein-- the cooling
assembly has a first length, the first balloon is elongated and has a
second length, the second balloon is elongated and has a third length,
and the first, second, and third lengths are generally parallel in the
deployed state.

19. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion having a length, the shaft being configured to locate the
distal portion intravascularly at a treatment site within or otherwise
proximate a renal artery or renal ostium; a supply lumen along at least a
portion of the shaft, the supply lumen being configured to receive liquid
refrigerant; an applicator at the distal portion of the shaft, the
applicator having a delivery state and a deployed state and including at
least a first chamber and a second chamber, the first chamber having a
heat-transfer portion in fluid communication with the supply lumen, and
wherein the heat-transfer portion extends around less than a full
circumference of the applicator in a plane perpendicular to the length; a
first exhaust assembly configured to transport refrigerant from the first
chamber such that the first chamber has a first heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant sufficient
to cause therapeutically-effective, cryogenic renal-nerve modulation; and
a second exhaust assembly configured to transport refrigerant from the
second chamber such that the second chamber has a second heat-transfer
rate in the deployed state while the cooling assembly receives
refrigerant less than the first heat-transfer rate, wherein the second
exhaust assembly is fluidly separate from the first exhaust assembly.

20. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion, the shaft being configured to locate the distal portion
intravascularly at a treatment site within or otherwise proximate a renal
artery or renal ostium; a supply lumen along at least a portion of the
shaft, the supply lumen being configured to receive liquid refrigerant;
and a cooling assembly at the distal portion of the shaft, the cooling
assembly having a delivery state and a deployed state, the cooling
assembly including an orifice and an applicator including a first balloon
and a second balloon, the orifice being in fluid communication with the
supply lumen, the first balloon having a helical heat-transfer portion
curving around the second balloon and in fluid communication with the
orifice, and the second balloon being at least partially collapsed in the
delivery state, wherein the heat-transfer portion has a heat-transfer
rate in the deployed state while the cooling assembly receives
refrigerant sufficient to cause therapeutically-effective, cryogenic
renal-nerve modulation.

21. The cryotherapeutic device of claim 20, wherein the first balloon is
generally non-compliant and the second balloon is generally compliant.

22. The cryotherapeutic device of claim 20, wherein the first balloon is
generally compliant and the second balloon is generally non-compliant.

23. The cryotherapeutic device of claim 20, wherein the first and second
balloons are generally compliant.

24. The cryotherapeutic device of claim 20, wherein the first and second
balloons are generally non-compliant.

25. The cryotherapeutic device of claim 20, wherein the heat-transfer
portion is a first heat-transfer portion, the heat-transfer rate is a
first heat-transfer rate, the second balloon has a second heat-transfer
portion having a second heat-transfer rate in the deployed state while
the cooling assembly receives refrigerant less than the first
heat-transfer rate.

26. The cryotherapeutic device of claim 20, wherein the applicator is
expandable and configured to completely occlude renal arteries or renal
ostiums having different cross-sectional dimensions.

27. The cryotherapeutic device of claim 20, wherein the heat-transfer
portion has a helical diameter, the second balloon is generally
compliant, and expanding the second balloon increases the helical
diameter in the deployed state.

28. The cryotherapeutic device of claim 20, wherein the first balloon
defines a first chamber, the second balloon defines a second chamber, the
first chamber is fluidly separate from the second chamber, the device
further comprises a filler lumen along at least a portion of the shaft,
and the filler lumen is configured to supply filler material to the
second chamber.

29. The cryotherapeutic device of claim 20, wherein the first balloon
includes a helical portion, the second balloon has a generally circular
cross-sectional dimension in the deployed state configured to occlude the
renal artery or renal ostium, and the helical portion wraps around the
second balloon.

30. The cryotherapeutic device of claim 20, wherein the second balloon
has an outer wall surface and the first balloon is at least partially
inset into the outer wall surface.

31. The cryotherapeutic device of claim 20, wherein the second balloon
has an inner wall surface and the first balloon is at the inner wall
surface.

32. The cryotherapeutic device of claim 20, wherein the first balloon
defines a first chamber, the second balloon defines a second chamber, the
first chamber is fluidly connected to the second chamber, and the second
chamber is configured to receive refrigerant from the first chamber.

33. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion, the shaft being configured to locate the distal portion
intravascularly at a treatment site within or otherwise proximate a renal
artery or renal ostium; a supply lumen along at least a portion of the
shaft, the supply lumen being configured to receive liquid refrigerant;
and an applicator at the distal portion, the applicator having a first
chamber in fluid communication with the supply lumen and a second
chamber, the first chamber having a heat-transfer portion in fluid
communication with the supply lumen, and the first chamber including a
helical portion curving around the second chamber, wherein the helical
portion has a heat-transfer rate in the deployed state while the cooling
assembly receives refrigerant sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation.

34. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion having a length, the shaft being configured to locate the
distal portion intravascularly at a treatment site within or otherwise
proximate a renal artery or renal ostium; a supply lumen along at least a
portion of the shaft, the supply lumen being configured to receive liquid
refrigerant; and a cooling assembly at the distal portion, the cooling
assembly having a delivery state and a deployed state, the cooling
assembly including an orifice and an applicator including a first helical
balloon and a second helical balloon, the orifice being in fluid
communication with the supply lumen and the first helical balloon, and
the first and second helical balloons being wound around a portion of the
shaft and at least partially intertwined, wherein the first helical
balloon has a first heat-transfer rate in the deployed state while the
cooling assembly receives refrigerant sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation, and wherein
the second helical balloon has a second heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant less than
the first heat-transfer rate.

35. The cryotherapeutic device of claim 34, wherein the device further
comprises an exhaust passage along at least a portion of the shaft and
wherein the first and second helical balloons wrap around the exhaust
passage.

36. The cryotherapeutic device of claim 34, wherein the first helical
balloon defines a first chamber, the second helical balloon defines a
second chamber, the first chamber is fluidly separate from the second,
the device further comprises a filler lumen along at least a portion of
the shaft, and the filler lumen is configured to supply filler material
to the second chamber.

37. The cryotherapeutic device of claim 34, wherein the first helical
balloon defines a first chamber, the second helical balloon defines a
second chamber, the first chamber is fluidly connected to the second
chamber and the second chamber is configured to receive refrigerant from
the first chamber.

38. The cryotherapeutic device of claim 34, wherein the applicator
includes a third helical balloon having a third heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant less than
the first heat-transfer rate, and wherein the third helical balloon is at
least partially intertwined with the first and second helical balloons.

39. The cryotherapeutic device of claim 38, wherein-- the cooling
assembly has a length, the first helical balloon has a first curved
portion, the second helical balloon has a second curved portion, the
third helical balloon has a third curved portion, and the second and
third curved portions are at opposite sides of the first curved portion
along the length.

40. The cryotherapeutic device of claim 38, wherein the first helical
balloon defines a first chamber, the second helical balloon defines a
second chamber, the third helical balloon defines a third chamber, the
first chamber is fluidly separate from the second and third chambers, the
device further comprises a filler lumen along at least a portion of the
shaft, and the filler lumen is configured to supply filler material to
the second chamber, the third chamber, or both.

41. The cryotherapeutic device of claim 38, wherein the first helical
balloon defines a first chamber, the second helical balloon defines a
second chamber, the third helical balloon defines a third chamber, the
first chamber is fluidly connected to the second and third chambers and
the second and third chambers are configured to receive refrigerant from
the first chamber.

42. The cryotherapeutic device of claim 34, wherein the applicator
includes a third helical balloon having a third heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant sufficient
to cause therapeutically-effective, cryogenic renal-nerve modulation, and
wherein the third helical balloon is least partially intertwined with the
first and second helical balloons.

43. The cryotherapeutic device of claim 42, wherein-- the cooling
assembly has a length, the first helical balloon has a first curved
portion, the second helical balloon has a second curved portion, the
third helical balloon has a third curved portion, and the first and third
curved portions are at opposite sides of the second curved portion along
the length.

44. The cryotherapeutic device of claim 42, wherein the first helical
balloon defines a first chamber, the second helical balloon defines a
second chamber, the third helical balloon defines a third chamber, the
second chamber is fluidly separate from the first and third chambers, the
device further comprises a filler lumen along at least a portion of the
shaft, and the filler lumen is configured to supply filler material to
the second chamber.

45. The cryotherapeutic device of claim 42, wherein the first helical
balloon defines a first chamber, the second helical balloon defines a
second chamber, the third helical balloon defines a third chamber, the
first and third chambers are fluidly connected to the second chamber and
the second chamber is configured to receive refrigerant from the first
chamber.

46. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion having a length, the shaft being configured to locate the
distal portion intravascularly at a treatment site within or otherwise
proximate a renal artery or renal ostium; a supply lumen along at least a
portion of the shaft, the supply lumen being configured to receive liquid
refrigerant; and an applicator at the distal portion, the applicator
having a delivery state and a deployed state and including a first
chamber and a second chamber, the first chamber having a heat-transfer
portion in fluid communication with the supply lumen, the first chamber
including a first generally-helical portion, the second chamber including
a second generally-helical portion, and the first and second
generally-helical portions being at least partially intertwined, wherein
the heat-transfer portion has a heat-transfer rate in the deployed state
while the cooling assembly receives refrigerant sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation, and wherein
the heat-transfer portion extends around less than a full circumference
of the applicator in a plane perpendicular to the length.

47. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion, the shaft being configured to locate the distal portion
intravascularly at a treatment site within or otherwise proximate a renal
artery or renal ostium; a supply lumen along at least a portion of the
shaft, the supply lumen being configured to receive liquid refrigerant; a
cooling assembly at the distal portion, the cooling assembly having a
delivery state and a deployed state, the cooling assembly including an
orifice and an applicator including a first balloon defining a first
chamber and a second balloon defining a second chamber, the orifice being
in fluid communication with the supply lumen, the first balloon having a
first heat-transfer portion in fluid communication with the orifice, the
second balloon having a second heat-transfer portion, the second balloon
being at least partially collapsed in the delivery state, the second
chamber being fluidly separate from the first chamber, wherein the first
heat-transfer portion has a first heat-transfer rate in the deployed
state while the cooling assembly receives refrigerant sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation, wherein the
second heat-transfer portion has a second heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant less than
the first heat-transfer rate, and wherein the first heat-transfer portion
is non-circumferential at longitudinal segments along the length of the
cooling assembly; and a filler lumen along at least a portion of the
shaft, the filler lumen being configured to supply a filler material to
the second chamber.

48. The cryotherapeutic device of claim 47, wherein the first balloon is
non-collapsible such that it has a fixed volume.

49. The cryotherapeutic device of claim 47, wherein the first
heat-transfer portion includes a metal heat-transfer member.

50. The cryotherapeutic device of claim 47, wherein the second balloon is
within the first balloon.

51. The cryotherapeutic device of claim 47, wherein-- the distal portion
has a length, the second balloon is configured to preferentially expand
generally in a first direction relative to the length, the orifice is
configured to direct expansion of refrigerant from the supply lumen
toward the first heat-transfer portion generally in a second direction
relative to the length, and an angle between the first direction and the
second direction is from about 15.degree. to about 180.degree..

52. The cryotherapeutic device of claim 47, wherein the second balloon
has an inner surface and the filler lumen is generally non-collapsible
and connected to the inner surface.

53. The cryotherapeutic device of claim 47, wherein the applicator is
expandable and configured to completely occlude renal arteries or renal
ostiums having different cross-sectional dimensions.

54. The cryotherapeutic device of claim 47, wherein the second balloon in
the deployed state is configured to thermally insulate a portion of the
treatment site from the first balloon.

55. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion having a length, the shaft being configured to locate the
distal portion intravascularly at a treatment site within or otherwise
proximate a renal artery or renal ostium; a supply lumen along at least a
portion of the shaft, the supply lumen being configured to receive liquid
refrigerant; an applicator at the distal portion, the applicator having a
delivery state and a deployed state and including a first chamber and a
second chamber, the first chamber having a first heat-transfer portion in
fluid communication with the supply lumen, the second chamber having a
second heat-transfer portion, and the second chamber being fluidly
separate from the first chamber, wherein the first heat-transfer portion
has a first heat-transfer rate in the deployed state while the cooling
assembly receives refrigerant sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation, wherein the
second heat-transfer portion has a second heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant less than
the first heat-transfer rate, and wherein the first heat-transfer portion
extends around less than a full circumference of the applicator in a
plane perpendicular to the length; and a filler lumen along at least a
portion of the shaft, the filler lumen being configured to supply filler
material to the second chamber.

56. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion, the shaft being configured to locate the distal portion
intravascularly at a treatment site within or otherwise proximate a renal
artery or renal ostium; a supply lumen along at least a portion of the
shaft, the supply lumen being configured to receive liquid refrigerant;
and a cooling assembly at the distal portion of the shaft, the cooling
assembly having a delivery state and a deployed state, the cooling
assembly including an orifice and an applicator including a first balloon
defining a first chamber and a second balloon defining a second chamber,
the orifice being in fluid communication with the supply lumen, the first
balloon having a first heat-transfer portion in fluid communication with
the orifice, the second balloon having a second heat-transfer portion,
the second balloon being at least partially collapsed in the delivery
state, the second chamber being fluidly connected to the first chamber,
wherein the second chamber is configured to receive refrigerant from the
first chamber, wherein the first heat-transfer portion has a first
heat-transfer rate in the deployed state while the cooling assembly
receives refrigerant sufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation, wherein the second heat-transfer
portion has a second heat-transfer rate in the deployed state while the
cooling assembly receives refrigerant less than the first heat-transfer
rate, and wherein the first heat-transfer portion is non-circumferential
at longitudinal segments along the length of the cooling assembly.

57. The cryotherapeutic device of claim 56, wherein the first chamber has
a first refrigerant residence time in the deployed state, the second
chamber has a second refrigerant residence time in the deployed state,
and the first refrigerant residence time is less than the second
refrigerant residence time.

58. The cryotherapeutic device of claim 56, wherein the device further
comprises an exhaust passage along at least a portion of the shaft and
the first and second chambers are fluidly connected to the exhaust
passage.

59. The cryotherapeutic device of claim 56, wherein the device further
comprises an exhaust passage along at least a portion of the shaft, the
exhaust passage has an exhaust-passage distal portion, and the first
chamber is fluidly connected to the second chamber through the
exhaust-passage distal portion.

60. The cryotherapeutic device of claim 56, wherein the second balloon is
configured to passively inflate with refrigerant from the first balloon.

61. The cryotherapeutic device of claim 56, wherein the applicator is
expandable and configured to completely occlude renal arteries or renal
ostiums having different cross-sectional dimensions.

62. The cryotherapeutic device of claim 56, wherein the second balloon in
the deployed state is configured to thermally insulate a portion of the
treatment site from the first balloon.

63. The cryotherapeutic device of claim 56, wherein-- the cooling
assembly has a first length, the first balloon is elongated and has a
second length, the second balloon is elongated and has a third length,
and the first, second, and third lengths are generally parallel in the
deployed state.

64. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion having a length, the shaft being configured to locate the
distal portion intravascularly at a treatment site within or otherwise
proximate a renal artery or renal ostium; a supply lumen along at least a
portion of the shaft, the supply lumen being configured to receive liquid
refrigerant; and an applicator at the distal portion, the applicator
having a delivery state and a deployed state and including a first
chamber and a second chamber, the first chamber having a first
heat-transfer portion in fluid communication with the supply lumen, the
second chamber having a second heat-transfer portion, and the second
chamber being fluidly connected to the first chamber, wherein the second
chamber is configured to receive refrigerant from the first chamber,
wherein the first heat-transfer portion has a first heat-transfer rate in
the deployed state while the cooling assembly receives refrigerant
sufficient to cause therapeutically-effective, cryogenic renal-nerve
modulation, wherein the second heat-transfer portion has a second
heat-transfer rate in the deployed state while the cooling assembly
receives refrigerant less than the first heat-transfer rate, and wherein
the first heat-transfer portion extends around less than a full
circumference of the applicator in a plane perpendicular to the length.

65. The cryotherapeutic device of claim 64, further comprising an exhaust
passage along at least a portion of the shaft, the exhaust passage being
configured to transport refrigerant from the first chamber, wherein the
second chamber is configured to transport refrigerant from the first
chamber to the exhaust passage.

66. The cryotherapeutic device of claim 65, wherein-- the first chamber
has a first-chamber distal portion and a first-chamber proximal portion
and is configured to transport refrigerant from the first-chamber
proximal portion to the first-chamber distal portion, the second chamber
has a second chamber distal portion and a second-chamber proximal portion
and is configured to transport refrigerant from the second-chamber distal
portion to the second-chamber proximal portion, the exhaust passage has
an exhaust-passage distal portion, and the second-chamber proximal
portion is proximate the exhaust-passage distal portion.

67. The cryotherapeutic device of claim 65, wherein the applicator has a
primary refrigerant flow path from the first chamber to the exhaust
passage and the primary refrigerant flow path passes through the second
chamber.

68. A cryotherapeutic device, comprising: an elongated shaft with a
distal portion having a length, the shaft being configured to locate the
distal portion intravascularly at a treatment site within or otherwise
proximate a renal artery or renal ostium; a supply lumen along at least a
portion of the shaft, the supply lumen being configured to receive liquid
refrigerant; an applicator at the distal portion of the shaft, the
applicator having a delivery state and a deployed state and including a
first chamber and a second chamber, and the first chamber having a
heat-transfer portion in fluid communication with the supply lumen,
wherein the heat-transfer portion has a heat-transfer rate in the
deployed state while the cooling assembly receives refrigerant sufficient
to cause therapeutically-effective, cryogenic renal-nerve modulation, and
wherein the heat-transfer portion extends around less than a full
circumference of the applicator in a plane perpendicular to the length;
and an exhaust passage along at least a portion of the shaft, the exhaust
passage being configured to transport refrigerant from the first chamber,
wherein the second chamber is configured to transport refrigerant from
the first chamber to the exhaust passage.

69. A method for treating a patient, comprising: locating an applicator
of a cooling assembly of a cryotherapeutic device intravascularly at a
treatment site within or otherwise proximate a renal artery or an ostium
of the renal artery, wherein the applicator is at a distal portion of an
elongated shaft; deploying the cooling assembly from a delivery state to
a deployed state, the applicator including a first balloon and a second
balloon, the second balloon being at least partially collapsed in the
delivery state; and cooling a portion of the treatment site through a
heat-transfer portion of the first balloon at a heat-transfer rate
sufficient to cause therapeutically-effective, cryogenic renal-nerve
modulation by transitioning liquid refrigerant into gaseous refrigerant
within the cooling assembly, the portion of the treatment site being
generally non-circumferential in generally any plane perpendicular to a
length of the renal artery.

70. A method for treating a patient, comprising: locating an applicator
of a cooling assembly of a cryotherapeutic device intravascularly at a
treatment site within or otherwise proximate a renal artery or an ostium
of the renal artery, wherein the applicator is at a distal portion of an
elongated shaft; deploying the cooling assembly from a delivery state to
a deployed state, the applicator including a first balloon and a second
balloon, the second balloon being at least partially collapsed in the
delivery state, wherein deploying the cooling assembly includes generally
non-compliantly expanding the first balloon and generally compliantly
expanding the second balloon; cooling a first portion of the treatment
site through a heat-transfer portion of the first balloon at a
heat-transfer rate sufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation by transitioning liquid refrigerant into
gaseous refrigerant within the cooling assembly, the first portion of the
treatment site being generally non-circumferential in generally any plane
perpendicular to a length of the renal artery; and thermally insulating a
second portion of the treatment site with the second balloon in the
deployed state.

71. The method of claim 70, wherein deploying the cooling assembly
includes expanding the applicator to span across a cross-sectional
dimension of the renal artery or the ostium of the renal artery.

72. The method of claim 70, wherein the first balloon defines a first
chamber, the second balloon defines a second chamber, and the method
further comprises introducing filler material into the second chamber
through a filler lumen along at least a portion of the shaft, wherein the
first chamber is fluidly separate from the second chamber.

73. The method of claim 72, wherein the filler material is biologically
inert.

74. A method for treating a patient, comprising: locating an applicator
of a cooling assembly of a cryotherapeutic device intravascularly at a
treatment site within or otherwise proximate a renal artery or an ostium
of the renal artery, wherein the applicator is at a distal portion of an
elongated shaft; deploying the cooling assembly from a delivery state to
a deployed state, the applicator including a first balloon defining a
first chamber and a second balloon defining a second chamber, the second
balloon being at least partially collapsed in the delivery state;
circulating gaseous refrigerant through the first chamber at a first
pressure; circulating gaseous refrigerant through the second chamber at a
second pressure different than the first pressure; cooling a first
portion of the treatment site through a first heat-transfer portion of
the first balloon at a first heat-transfer rate sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation by
transitioning liquid refrigerant into gaseous refrigerant within the
cooling assembly, the first portion of the treatment site being generally
non-circumferential in generally any plane perpendicular to a length of
the renal artery; and cooling a second portion of the treatment site
through a second heat-transfer portion of the second balloon at a second
heat-transfer rate less than the first heat-transfer rate.

75. The method of claim 74, wherein the first heat-transfer rate is
generally surface-area limited and the second heat-transfer rate is
generally refrigerant limited.

76. The method of claim 74, further comprising regulating the first
pressure and the second pressure.

77. A method for treating a patient, comprising: locating an applicator
of a cooling assembly of a cryotherapeutic device intravascularly at a
treatment site within or otherwise proximate a renal artery or an ostium
of the renal artery, wherein the applicator is at a distal portion of an
elongated shaft; deploying the cooling assembly from a delivery state to
a deployed state, the applicator including a first balloon and a second
balloon, the first balloon including a helical portion at least partially
wrapped around the second balloon, and the second balloon being at least
partially collapsed in the delivery state; and cooling a portion of the
treatment site through a heat-transfer portion of the first balloon at a
heat-transfer rate sufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation by transitioning liquid refrigerant into
gaseous refrigerant within the cooling assembly, the portion of the
treatment site being generally non-circumferential in generally any plane
perpendicular to a length of the renal artery.

78. The method of claim 77, wherein deploying the cooling assembly
includes expanding the applicator to span across a cross-sectional
dimension of the renal artery or the ostium of the renal artery.

79. The method of claim 77, wherein deploying the cooling assembly
includes generally compliantly expanding the second balloon to increase a
helical diameter of the helical portion.

80. The method of claim 77, further comprising: exhausting gaseous
refrigerant from the first balloon; and supplying gaseous refrigerant
from the first balloon to the second balloon.

81. A method for treating a patient, comprising: locating an applicator
of a cooling assembly of a cryotherapeutic device intravascularly at a
treatment site within or otherwise proximate a renal artery or an ostium
of the renal artery, wherein the applicator is at a distal portion of an
elongated shaft; deploying the cooling assembly from a delivery state to
a deployed state, the applicator including a first balloon and a second
balloon, the first balloon including a first helical portion, the second
balloon including a second helical portion, and the first and second
helical portions being at least partially intertwined; cooling a first
portion of the treatment site through a heat-transfer portion of the
first balloon at a heat-transfer rate sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation by
transitioning liquid refrigerant into gaseous refrigerant within the
cooling assembly, the first portion of the treatment site being generally
non-circumferential in generally any plane perpendicular to a length of
the renal artery; and thermally insulating a second portion of the
treatment site with the second balloon in the deployed state.

82. The method of claim 81, further comprising: exhausting gaseous
refrigerant from the first balloon; and supplying gaseous refrigerant
from the first balloon to the second balloon.

83. The method of claim 81, wherein deploying the cooling assembly
includes expanding the applicator to span across a cross-sectional
dimension of the renal artery or the ostium of the renal artery.

84. The method of claim 81, wherein the first balloon defines a first
chamber, the second balloon defines a second chamber, and the method
further comprises introducing filler material into the second chamber
intravascularly through a filler lumen along at least a portion of the
shaft, wherein the first chamber is fluidly separate from the second
chamber.

85. The method of claim 84, wherein the filler material is biologically
inert.

86. A method for treating a patient, comprising: locating an applicator
of a cooling assembly of a cryotherapeutic device intravascularly at a
treatment site within or otherwise proximate a renal artery or an ostium
of the renal artery, wherein the applicator is at a distal portion of an
elongated shaft; deploying the cooling assembly from a delivery state to
a deployed state, the applicator including a first balloon defining a
first chamber and a second balloon defining a second chamber, the second
chamber being at least partially collapsed in the delivery state; cooling
a first portion of the treatment site through a heat-transfer portion of
the first balloon at a heat-transfer rate sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation by
transitioning liquid refrigerant into gaseous refrigerant within the
cooling assembly, the first portion of the treatment site being generally
non-circumferential in generally any plane perpendicular to a length of
the renal artery; introducing filler material into the second chamber
intravascularly through a filler lumen along at least a portion of the
shaft, wherein the first chamber is fluidly separate from the second
chamber; and thermally insulating a second portion of the treatment site
with the second balloon in the deployed state.

87. The method of claim 86, wherein the filler material is biologically
inert.

88. The method of claim 86, wherein cooling the first portion of the
treatment site includes cooling the first portion of the treatment site
through a metal heat-transfer member of the heat-transfer portion.

89. The method of claim 86, wherein the second balloon is within the
first balloon and introducing filler material into the second chamber
increases an amount of space that the second balloon occupies within the
first balloon.

90. The method of claim 86, wherein deploying the cooling assembly
includes expanding the applicator to span across a cross-sectional
dimension of the renal artery or the ostium of the renal artery.

91. The method of claim 86, further comprising preferentially expanding
the second balloon in a first direction relative to a length of the
cooling assembly, wherein transitioning liquid refrigerant into gaseous
refrigerant includes directing expansion of refrigerant toward the
heat-transfer portion generally in a second direction relative to the
length, and an angle between the first direction and the second direction
is from about 15.degree. to about 180.degree..

92. A method for treating a patient, comprising: locating an applicator
of a cooling assembly of a cryotherapeutic device intravascularly at a
treatment site within or otherwise proximate a renal artery or an ostium
of the renal artery, wherein the applicator is at a distal portion of an
elongated shaft; deploying the cooling assembly from a delivery state to
a deployed state, the applicator including a first balloon defining a
first chamber and a second balloon defining a second chamber, the second
balloon being at least partially collapsed in the delivery state; cooling
a first portion of the treatment site through a heat-transfer portion of
the first balloon at a heat-transfer rate sufficient to cause
therapeutically-effective, cryogenic renal-nerve modulation by
transitioning liquid refrigerant into gaseous refrigerant within the
cooling assembly, the first portion of the treatment site being generally
non-circumferential in generally any plane perpendicular to a length of
the renal artery; thermally insulating a second portion of the treatment
site with the second balloon in the deployed state; exhausting gaseous
refrigerant from the first chamber; and supplying gaseous refrigerant
from the first chamber to the second chamber.

93. The method of claim 92, wherein deploying the cooling assembly
includes expanding the applicator to span across a cross-sectional
dimension of the renal artery or the ostium of the renal artery.

94. The method of claim 92, wherein supplying gaseous refrigerant from
the first chamber to the second chamber includes passively inflating the
second balloon with gaseous refrigerant.

95. The method of claim 92, wherein supplying gaseous refrigerant from
the first chamber to the second chamber includes supplying gaseous
refrigerant through a distal portion of an exhaust passage along at least
a portion of the shaft, the exhaust passage being configured to transport
gaseous refrigerant from the first chamber.

96. The method of claim 92, further comprising: circulating gaseous
refrigerant within the first chamber at a first refrigerant residence
time; and circulating gaseous refrigerant within the second chamber at a
second refrigerant residence time, wherein the first refrigerant
residence time is less than the second refrigerant residence time.

97. The method of claim 92, wherein supplying gaseous refrigerant from
the first chamber to the second chamber includes transporting gaseous
refrigerant from the first chamber to an exhaust passage, the exhaust
passage being along at least a portion of the shaft.

98. The method of claim 97, further comprising: transporting gaseous
refrigerant from a proximal portion of the first chamber to a distal
portion of the first chamber; transporting gaseous refrigerant from the
distal portion of the first chamber to a distal portion of the second
chamber; and transporting gaseous refrigerant from the distal portion of
the second chamber to a proximal portion of the second chamber.

99. The method of claim 97, wherein exhausting gaseous refrigerant from
the first chamber includes exhausting gaseous refrigerant from the first
chamber along a primary gaseous-refrigerant flow path, and the primary
gaseous-refrigerant flow path passes through the second chamber.

[0006] All of the foregoing applications are incorporated herein by
reference in their entireties. Further, components and features of
embodiments disclosed in the applications incorporated by reference may
be combined with various components and features disclosed and claimed in
the present application

RELATED APPLICATIONS INCORPORATED BY REFERENCE

[0007] U.S. Provisional Application No. 61/545,052, filed Oct. 7, 2011,
U.S. patent application Ser. No. 13/204,504, filed Aug. 5, 2011, PCT
International Application No. PCT/US2011/46845, filed Aug. 5, 2011, and
U.S. Provisional Application No. 61/371,110, filed Aug. 5, 2010, are
related to the present application, and the foregoing applications are
incorporated herein by reference in their entireties. As such, components
and features of embodiments disclosed in the applications incorporated by
reference may be combined with various components and features disclosed
and claimed in the present application.

TECHNICAL FIELD

[0008] The present technology relates generally to cryotherapeutic
devices. In particular, several embodiments are directed to
cryotherapeutic devices for intravascular neuromodulation and associated
systems and methods.

BACKGROUND

[0009] The sympathetic nervous system (SNS) is a primarily involuntary
bodily control system typically associated with stress responses. Fibers
of the SNS innervate tissue in almost every organ system of the human
body and can affect characteristics such as pupil diameter, gut motility,
and urinary output. Such regulation can have adaptive utility in
maintaining homeostasis or in preparing the body for rapid response to
environmental factors. Chronic activation of the SNS, however, is a
common maladaptive response that can drive the progression of many
disease states. Excessive activation of the renal SNS in particular has
been identified experimentally and in humans as a likely contributor to
the complex pathophysiology of hypertension, states of volume overload
(such as heart failure), and progressive renal disease. For example,
radiotracer dilution has demonstrated increased renal norepinephrine (NE)
spillover rates in patients with essential hypertension.

[0010] Cardio-renal sympathetic nerve hyperactivity can be particularly
pronounced in patients with heart failure. For example, an exaggerated NE
overflow from the heart and kidneys to plasma is often found in these
patients. Heightened SNS activation commonly characterizes both chronic
and end stage renal disease. In patients with end stage renal disease, NE
plasma levels above the median have been demonstrated to be predictive
for cardiovascular diseases and several causes of death. This is also
true for patients suffering from diabetic or contrast nephropathy.
Evidence suggests that sensory afferent signals originating from diseased
kidneys are major contributors to initiating and sustaining elevated
central sympathetic outflow.

[0011] Sympathetic nerves to the kidneys terminate in the blood vessels,
the juxtaglomerular apparatus, and the renal tubules. Stimulation of the
renal sympathetic nerves can cause increased renin release, increased
sodium (Na.sup.+) reabsorption, and a reduction of renal blood flow.
These neural regulation components of renal function are considerably
stimulated in disease states characterized by heightened sympathetic tone
and likely contribute to increased blood pressure in hypertensive
patients. The reduction of renal blood flow and glomerular filtration
rate as a result of renal sympathetic efferent stimulation is likely a
cornerstone of the loss of renal function in cardio-renal syndrome (i.e.,
renal dysfunction as a progressive complication of chronic heart
failure). Pharmacologic strategies to thwart the consequences of renal
efferent sympathetic stimulation include centrally acting sympatholytic
drugs, beta blockers (intended to reduce renin release), angiotensin
converting enzyme inhibitors and receptor blockers (intended to block the
action of angiotensin II and aldosterone activation consequent to renin
release), and diuretics (intended to counter the renal sympathetic
mediated sodium and water retention). These pharmacologic strategies,
however, have significant limitations including limited efficacy,
compliance issues, side effects, and others. Accordingly, there is a
strong public-health need for alternative treatment strategies.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Many aspects of the present disclosure can be better understood
with reference to the following drawings. The components in the drawings
are not necessarily to scale. Instead, emphasis is placed on illustrating
clearly the principles of the present disclosure. Furthermore, components
can be shown as transparent in certain views for clarity of illustration
only and not to indicate that the illustrated component is necessarily
transparent.

[0013]FIG. 1 illustrates a cryotherapeutic system in accordance with an
embodiment of the present technology.

[0014]FIG. 2A is an enlarged cross-sectional view illustrating an
embodiment of a distal portion of a shaft and a cooling assembly in a
delivery state (e.g., low-profile or collapsed configuration) in
accordance with an embodiment of the present technology.

[0015]FIG. 2B is an enlarged cross-sectional view of the cooling assembly
of FIG. 2A in a deployed stated (e.g., expanded configuration).

[0016] FIGS. 2C and 2D are enlarged side and end cross-sectional views of
a cooling assembly configured in accordance with another embodiment of
the present technology.

[0017] FIG. 2E is an enlarged cross-sectional view of proximal and distal
portions of a cryotherapeutic device configured in accordance with yet
another embodiment of the present technology.

[0018]FIG. 3A illustrates cryogenically modulating renal nerves with a
cryotherapeutic system in accordance with an embodiment of the
technology.

[0019]FIG. 3B is a block diagram illustrating a method of cryogenically
modulating renal nerves in accordance with any embodiment of the present
technology.

[0020] FIGS. 4A and 4B are enlarged cross-sectional views of
cryotherapeutic devices having stepped distal end portions configured in
accordance with embodiments of the present technology.

[0021]FIG. 5A is a partially schematic view of a cryotherapeutic system
configured in accordance with another embodiment of the present
technology.

[0022]FIG. 5B is an enlarged cross-sectional view of a distal portion of
a shaft and a cooling assembly in a deployed state in accordance with an
embodiment of the present technology.

[0023]FIG. 6A is a plan view illustrating a pre-cooling assembly
configured in accordance with an embodiment of the present technology.

[0024]FIG. 6B is a cross-sectional view illustrating the pre-cooling
assembly of FIG. 6A.

[0025]FIG. 7 is a cross-sectional view illustrating a pre-cooling
assembly having a valve configured in accordance with an embodiment of
the present technology.

[0026]FIG. 8A is a cross-sectional view illustrating a pre-cooling
assembly having a flow separator configured in accordance with an
embodiment of the present technology.

[0027]FIG. 8B is a cross-sectional view illustrating the pre-cooling
assembly of FIG. 8A.

[0028]FIG. 9A is a cross-sectional view illustrating a pre-cooling
assembly having a flow separator configured in accordance with another
embodiment of the present technology.

[0029]FIG. 9B is a cross-sectional view illustrating the pre-cooling
assembly of FIG. 9A.

[0030]FIG. 10 is a partially schematic view illustrating a tubular member
of a pre-cooling assembly coiled around an exhaust portal within a handle
configured in accordance with an embodiment of the present technology.

[0031]FIG. 11 is a partially schematic view illustrating a tubular member
of a pre-cooling assembly coiled near an exhaust portal within a handle
configured in accordance with an embodiment of the present technology.

[0032]FIG. 12 is a cross-sectional view illustrating a cooling assembly
having supply tubes with angled distal portions configured in accordance
with an embodiment of the present technology.

[0033] FIG. 13 is a cross-sectional view illustrating a cooling assembly
having a supply tube with a helical portion wrapped around an exhaust
passage configured in accordance with an embodiment of the present
technology.

[0034]FIG. 14 is a cross-sectional view illustrating a cooling assembly
having a supply tube with a helical portion wrapped around an exhaust
passage configured in accordance with another embodiment of the present
technology.

[0035] FIG. 15A is a cross-sectional view illustrating a cooling assembly
having an inner balloon with inner-balloon orifices configured in
accordance with an embodiment of the present technology.

[0036]FIG. 15B is a cross-sectional view illustrating the cooling
assembly of FIG. 15A.

[0037]FIG. 16A is a cross-sectional view illustrating a cooling assembly
having an inner balloon with inner-balloon orifices and an outer balloon
with a raised helical portion configured in accordance with an embodiment
of the present technology.

[0038]FIG. 16B is a cross-sectional view illustrating the cooling
assembly of FIG. 16A.

[0039]FIG. 17A is a cross-sectional view illustrating a cooling assembly
having elongated, thermally-insulative members configured in accordance
with an embodiment of the present technology.

[0045]FIG. 20A is a profile view illustrating a cooling assembly having a
thermally-insulative member resembling an intertwined double helix
configured in accordance with an embodiment of the present technology.

[0047] FIG. 21A is a cross-sectional view illustrating a cooling assembly
having elongated, thermally-insulative members movable within a balloon
configured in accordance with another embodiment of the present
technology.

[0049]FIG. 21c is a cross-sectional view illustrating the cooling
assembly of FIG. 21A in a delivery state within a delivery sheath.

[0050] FIG. 22A is a cross-sectional view illustrating a cooling assembly
having elongated, thermally-insulative members movable within a balloon
configured in accordance with an embodiment of the present technology.

[0051]FIG. 22B is a cross-sectional view illustrating the cooling
assembly of FIG. 22A.

[0052]FIG. 23A is a profile view illustrating a cooling assembly having
multiple partially-circumferential balloons configured in accordance with
an embodiment of the present technology.

[0053]FIG. 23B is an isometric view illustrating the cooling assembly of
FIG. 23A.

[0054]FIG. 24A is a profile view illustrating a cooling assembly having
multiple partially-circumferential balloons configured in accordance with
another embodiment of the present technology.

[0055]FIG. 24B is an isometric view illustrating the cooling assembly of
FIG. 24A.

[0056]FIG. 25 is a profile view illustrating a cooling assembly having a
helical recess configured in accordance with an embodiment of the present
technology.

[0057]FIG. 26 is a profile view illustrating a cooling assembly having
spaced apart recesses configured in accordance with an embodiment of the
present technology.

[0058]FIG. 27A is a profile view illustrating a cooling assembly having
spaced apart recesses configured in accordance with another embodiment of
the present technology.

[0069]FIG. 33D is a cross-sectional view illustrating the cooling
assembly of FIG. 33A in a delivery state within a delivery sheath.

[0070]FIG. 34 is a cross-sectional view illustrating a cooling assembly
having a balloon curved along its length configured in accordance with
another embodiment of the present technology.

[0071] FIG. 35A is a profile view illustrating a cooling assembly having a
balloon having a constrained longitudinal portion configured in
accordance with an embodiment of the present technology.

[0072]FIG. 35B is a cross-sectional view illustrating the cooling
assembly of FIG. 35A.

[0073]FIG. 36 is a cross-sectional view illustrating a cooling assembly
having a balloon having a constrained longitudinal portion configured in
accordance with another embodiment of the present technology.

[0074]FIG. 37 is a profile view illustrating a cooling assembly having a
looped balloon configured in accordance with an embodiment of the present
technology.

[0075]FIG. 38A is a profile view illustrating a cooling assembly having
multiple elongated balloons configured in accordance with an embodiment
of the present technology.

[0076]FIG. 38B is a cross-sectional view illustrating the cooling
assembly of FIG. 38A.

[0077]FIG. 39A is a profile view illustrating a cooling assembly having
multiple elongated balloons configured in accordance with another
embodiment of the present technology.

[0084]FIG. 43C is a profile view illustrating the cooling assembly of
FIG. 43A with the shaping member retracted.

[0085] FIG. 44A is a profile view illustrating a cooling assembly having
multiple elongated balloons attached to a shaping member configured in
accordance with another embodiment of the present technology.

[0086]FIG. 44B is a cross-sectional view illustrating the cooling
assembly of FIG. 44A.

[0087]FIG. 44C is a profile view illustrating the cooling assembly of
FIG. 44A with the shaping member retracted.

[0088]FIG. 45A is a profile view illustrating a cooling assembly having
multiple elongated balloons of different composition configured in
accordance with an embodiment of the present technology.

[0089]FIG. 45B is a cross-sectional view illustrating the cooling
assembly of FIG. 45A expanded to a first cross-sectional dimension.

[0091] FIG. 45C is a cross-sectional view illustrating the cooling
assembly of FIG. 45A expanded to a second cross-sectional dimension,
larger than the first cross-sectional dimension.

[0092]FIG. 46 is a cross-sectional view illustrating a cooling assembly
having multiple elongated balloons of different composition configured in
accordance with another embodiment of the present technology.

[0094]FIG. 47 is a profile view illustrating a cooling assembly having a
helical primary balloon wrapped around a secondary balloon configured in
accordance with an embodiment of the present technology.

[0095] FIG. 48A is a profile view illustrating a cooling assembly having a
helical primary balloon within a secondary balloon configured in
accordance with an embodiment of the present technology.

[0096]FIG. 48B is a cross-sectional view illustrating the cooling
assembly of FIG. 48A.

[0097]FIG. 49 is a profile view illustrating a cooling assembly having a
helical primary balloon wrapped around a secondary balloon configured in
accordance with another embodiment of the present technology.

[0098]FIG. 50 is a profile view illustrating a cooling assembly having a
helical primary balloon wrapped around a secondary balloon configured in
accordance with another embodiment of the present technology.

[0099]FIG. 51 is a profile view illustrating a cooling assembly having a
helical primary balloon wrapped around a secondary balloon configured in
accordance with another embodiment of the present technology.

[0100] FIG. 52A is a profile view illustrating a distal portion of a
cryotherapeutic device including a cooling assembly and an occlusion
member configured in accordance with an embodiment of the present
technology.

[0101]FIG. 52B is a cross-sectional view illustrating the distal portion
of FIG. 52A.

[0102]FIG. 53 is a cross-sectional view illustrating a distal portion of
a cryotherapeutic device including a cooling assembly and an occlusion
member configured in accordance with another embodiment of the present
technology.

[0103] FIG. 54 is a cross-sectional view illustrating a cooling assembly
that can be well-suited for circulation of refrigerant without phase
change configured in accordance with an embodiment of the present
technology.

[0104]FIG. 55 is a cross-sectional view illustrating a cooling assembly
that can be well-suited for circulation of refrigerant without phase
change configured in accordance with another embodiment of the present
technology.

[0105] FIG. 56 is a conceptual illustration of the sympathetic nervous
system (SNS) and how the brain communicates with the body via the SNS.

[0106] FIG. 57 is an enlarged anatomic view of nerves innervating a left
kidney to form the renal plexus surrounding the left renal artery.

[0107] FIGS. 58A and 58B are anatomic and conceptual views, respectively,
of a human body depicting neural efferent and afferent communication
between the brain and kidneys.

[0108] FIGS. 59A and 59B are anatomic views of the arterial vasculature
and venous vasculature, respectively, of a human.

DETAILED DESCRIPTION

[0109] Specific details of several embodiments of the technology are
described below with reference to FIGS. 1-59B. Although many of the
embodiments are described below with respect to devices, systems, and
methods for intravascular modulation of renal nerves using
cryotherapeutic approaches, other applications and other embodiments in
addition to those described herein are within the scope of the
technology. Additionally, several other embodiments of the technology can
have different configurations, components, or procedures than those
described herein. A person of ordinary skill in the art, therefore, will
accordingly understand that the technology can have other embodiments
with additional elements, or the technology can have other embodiments
without several of the features shown and described below with reference
to FIGS. 1-59B.

[0110] With regard to the terms "distal" and "proximal" within this
description, unless otherwise specified, the terms can reference a
relative position of the portions of a cryotherapeutic device and/or an
associated delivery device with reference to an operator and/or a
location in the vasculature. For example, proximal can refer to a
position closer to the operator of the device or an incision into the
vasculature, and distal can refer to a position that is more distant from
the operator of the device or further from the incision along the
vasculature.

Renal Neuromodulation

[0111] Renal neuromodulation is the partial or complete incapacitation or
other effective disruption of nerves innervating the kidneys. In
particular, renal neuromodulation comprises inhibiting, reducing, and/or
blocking neural communication along neural fibers (i.e., efferent and/or
afferent nerve fibers) innervating the kidneys. Such incapacitation can
be long-term (e.g., permanent or for periods of months, years, or
decades) or short-term (e.g., for periods of minutes, hours, days, or
weeks). Renal neuromodulation is expected to efficaciously treat several
clinical conditions characterized by increased overall sympathetic
activity, and in particular conditions associated with central
sympathetic overstimulation such as hypertension, heart failure, acute
myocardial infarction, metabolic syndrome, insulin resistance, diabetes,
left ventricular hypertrophy, chronic and end stage renal disease,
inappropriate fluid retention in heart failure, cardio-renal syndrome,
and sudden death. The reduction of afferent neural signals contributes to
the systemic reduction of sympathetic tone/drive, and renal
neuromodulation is expected to be useful in treating several conditions
associated with systemic sympathetic overactivity or hyperactivity. Renal
neuromodulation can potentially benefit a variety of organs and bodily
structures innervated by sympathetic nerves. For example, a reduction in
central sympathetic drive may reduce insulin resistance that afflicts
patients with metabolic syndrome and Type II diabetics. Additionally,
osteoporosis can be sympathetically activated and might benefit from the
downregulation of sympathetic drive that accompanies renal
neuromodulation. A more detailed description of pertinent patient anatomy
and physiology is provided below.

[0112] Various techniques can be used to partially or completely
incapacitate neural pathways, such as those innervating the kidneys.
Cryotherapy, for example, includes cooling tissue at a target site in a
manner that modulates neural function. The mechanisms of cryotherapeutic
tissue damage include, for example, direct cell injury (e.g., necrosis),
vascular injury (e.g., starving the cell from nutrients by damaging
supplying blood vessels), and sublethal hypothermia with subsequent
apoptosis. Exposure to cryotherapeutic cooling can cause acute cell death
(e.g., immediately after exposure) and/or delayed cell death (e.g.,
during tissue thawing and subsequent hyperperfusion). Several embodiments
of the present technology include cooling a structure at or near an inner
surface of a renal artery wall such that proximate (e.g., adjacent)
tissue is effectively cooled to a depth where sympathetic renal nerves
reside. For example, the cooling structure is cooled to the extent that
it causes therapeutically effective, cryogenic renal-nerve modulation.
Sufficiently cooling at least a portion of a sympathetic renal nerve is
expected to slow or potentially block conduction of neural signals to
produce a prolonged or permanent reduction in renal sympathetic activity.

[0113] Cryotherapy has certain characteristics that can be beneficial for
intravascular renal neuromodulation. For example, rapidly cooling tissue
provides an analgesic effect such that cryotherapies may be less painful
than ablating tissue at high temperatures. Cryotherapies may thus require
less analgesic medication to maintain patient comfort during a procedure
compared to heat ablation procedures. Additionally, reducing pain
mitigates patient movement and thereby increases operator success and
reduces procedural complications. Cryotherapy also typically does not
cause significant collagen tightening, and thus cryotherapy is not
typically associated with vessel stenosis.

[0114] Cryotherapies generally operate at temperatures that cause
cryotherapeutic applicators to adhere to moist tissue. This can be
beneficial because it promotes stable, consistent, and continued contact
during treatment. The typical conditions of treatment can make this an
attractive feature because, for example, a patient can move during
treatment, a catheter associated with an applicator can move, and/or
respiration can cause the kidneys to rise and fall and thereby move the
renal arteries. In addition, blood flow is pulsatile and causes the renal
arteries to pulse. Adhesion associated with cryotherapeutic cooling also
can be advantageous when treating short renal arteries in which stable
intravascular positioning can be more difficult to achieve.

Selected Embodiments of Renal Cryogenic Systems

[0115]FIG. 1 illustrates a cryotherapeutic system 100 configured in
accordance with several embodiments of the present technology. The
cryotherapeutic system 100 can include a console 102 and a
cryotherapeutic device 120. In the embodiment shown in FIG. 1, the
console 102 includes a supply container 104, a refrigerant 106 in the
supply container 104, and a supply control valve 108 in fluid
communication with the supply container 104. The supply container 104 can
be a single-use cartridge or a larger container that contains a
sufficient volume of refrigerant 106 to perform multiple procedures. The
larger supply containers, for example, can be refillable cylinders. The
supply container 104 is configured to retain the refrigerant 106 at a
desired pressure. For example, in one embodiment, liquid N2O is
contained in the supply container 104 at a pressure of 750 psi or greater
so it is in at least a substantially liquid state at ambient
temperatures. In other embodiments, the refrigerant 106 can include
carbon dioxide, a hydrofluorocarbon ("HFC"; e.g., Freon®, R-410A,
etc.), and/or other suitable compressed or condensed refrigerants that
can be retained in the supply container 104 at a sufficiently high
pressure to maintain the refrigerant 106 in at least a substantially
liquid state at ambient temperatures (e.g., approximately 210 psi for
R-410A).

[0116] The supply control valve 108 is coupled to a supply line 110
configured to transport the refrigerant 106 to the cryotherapeutic device
120. The supply control valve 108 can be operated manually or
automatically. The console 102 can optionally include a pump 111, such as
a vacuum pump or a DC power pump, and/or a backpressure control valve 113
coupled to an exhaust line 115 configured to receive exhausted
refrigerant 117 from the cryotherapeutic device 120. The pump 111 can
reduce the backpressure of evaporated refrigerant and, in conjunction
with the supply flow rate, increase refrigeration power. In other
embodiments, the expanded refrigerant 117 can exhaust to ambient
pressure.

[0117] The console 102 can further include an optional controller 118 that
operates the supply control valve 108 and the backpressure control valve
113. The controller 118, for example, can be a processor or dedicated
circuitry that implements a computerized algorithm for executing a
procedure automatically. The console 102 may also include an optional
user interface that receives user input and/or provides information to
the user and/or circuitry for monitoring optional sensors (e.g., pressure
or temperature) if present in the cryotherapeutic device 120. In one
embodiment, the controller 118 operates the backpressure control valve
113 to control the amount of vacuum applied to the exhausted refrigerant
117 returning from the cryotherapeutic device 120. This modulates the
backpressure of the evaporated refrigerant to control the temperature in
the cryotherapeutic device 120. In another embodiment, the supply control
valve 108 and/or the backpressure control valve 113 can be used to
increase the backpressure of exhausted refrigerant 117. Increasing the
backpressure of exhausted refrigerant 117 could increase the boiling
point of the refrigerant. For example, in the case of N2O, a slight
increase in backpressure from 1 atm to about 2 atm would raise the
boiling point from about 88° C. to about -75° C.; an
increase in backpressure to 3 atm would raise the boiling point to about
-65° C.

[0118] In certain embodiments, the cryotherapeutic system 100 may also
precool the refrigerant 106 to provide greater refrigeration power in the
refrigerant 106 by the time it reaches the cooling system. The system
100, for example, can include a precooler 119 (shown in dashed lines) in
the console 102. In other embodiments, the system 100 can include a
precooler along the supply line 110, at a handle at a proximal region of
the system 100, or elsewhere coupled to the cryotherapeutic device 120.

[0119] The cryotherapeutic device 120 includes a shaft 122 that has a
proximal portion 124, a handle 125 at a proximal region of the proximal
portion 124, and a distal portion 126 extending distally relative to the
proximal portion 124. The cryotherapeutic device 120 can further include
a cooling assembly 130 at the distal portion 126 of the shaft 122. The
shaft 122 is configured to locate the distal portion 126 intravascularly
at a treatment site proximate (e.g., in or near) a renal artery or renal
ostium, and the cooling assembly 130 is configured to provide
therapeutically-effective cryogenic renal-nerve modulation.

[0120]FIG. 2A is an enlarged cross-sectional view illustrating an
embodiment of the distal portion 126 of the shaft 122 and the cooling
assembly 130 in a delivery state (e.g., low-profile or collapsed
configuration), and FIG. 2B is an enlarged cross-sectional view of the
cooling assembly 130 in a deployed stated (e.g., expanded configuration).
In the embodiment shown in FIG. 2A, the distal portion 126 of the shaft
122 can include a first zone 127a and a second zone 127b (separated by
broken lines) recessed inwardly relative to the first zone 127a. The
first zone 127a can be demarcated from the second zone 127b by a step
128, such as a rabbet (e.g., an annular or other circumferential groove
configured to be fitted with another member). The first zone 127a can
accordingly have a first outer dimension or first cross-sectional
dimension (e.g., area or diameter), and the second zone 127b can have a
second outer dimension or second cross-sectional dimension less than the
first dimension. The shaft 122 can be sized to fit within a sheath 150 of
8 Fr or smaller (e.g., a 6 Fr guide sheath) to accommodate small renal
arteries.

[0121] The cryotherapeutic device 120 can also include a supply tube or
lumen 132 and an exhaust tube or lumen 134 along at least a portion of
the shaft 122. The supply lumen 132 can be a small tube configured to
retain the refrigerant in a liquid state at a high pressure. The inner
diameter of the supply lumen 132 is selected such that at least a portion
of the refrigerant reaching the cooling assembly 130 is in a liquid state
at a distal end 135 of the supply lumen 132. The exhaust lumen 134 can be
an outer tube, and the supply lumen 132 can extend within the exhaust
lumen 134 along at least the distal portion 126 of the shaft. As
described in further detail below, several embodiments of the
cryotherapeutic device 120 can further include one or more sensors 138,
such as a temperature sensor or pressure sensor, coupled to the
controller 118 (FIG. 1) by a lead 139. In several embodiments, the
cryotherapeutic system 100 can be configured to verify the proper
calibration of the sensors 138 before a cryotherapeutic treatment. For
example, the cryotherapeutic system 100 can automatically compare a
measured temperature from a temperature sensor with room temperature as
the cryotherapeutic system 100 initiates a power up cycle to check that
the temperature sensor is functioning properly.

[0122] The embodiment of the cooling assembly 130 shown in FIGS. 2A and 2B
can have an applicator 140 including a balloon 142 or other type of
expandable member that defines an expansion chamber configured to fully
occlude a renal artery or renal ostium. The balloon 142 can be relatively
short (e.g., 10 mm or less) to accommodate the length and tortuosity of a
renal artery (e.g., between 4-6 cm) and can have a diameter in an
expanded configuration large enough to contact a significant portion of
the inner circumference of the renal artery (e.g., between 3-10 mm in
diameter). In other embodiments described below, balloons can be
configured to only partially occlude a renal artery or renal ostium. The
balloon 142 can comprise a compliant material, a non-compliant material,
and/or a combination of compliant and non-compliant materials. In various
embodiments, for example, the balloon 142 can be made from polyurethane
and/or other compliant or semi-compliant materials that can expand and
conform to vessel walls to fully occlude vessels of varying sizes (e.g.,
vessels having an inner diameter from approximately 3 mm to approximately
10 mm, or in specific applications approximately 4 mm to approximately 8
mm). In other embodiments, the balloon 142 can be made from nylon and/or
other non-compliant materials and sized to accommodate vessels within a
certain size range. For example, a non-compliant nylon balloon can be
sized to accommodate vessels having an inner diameter between
approximately 3 mm and 6 mm, and a larger non-compliant nylon balloon can
be sized to accommodate vessels having an inner diameter between
approximately 7 mm and 10 mm.

[0123] In the embodiment illustrated in FIGS. 2A and 2B, the distal
portion of the balloon 142 is not connected to a support member (e.g.,
the supply lumen 132 and/or other support), and can therefore be dip
molded and/or otherwise formed to have a continuous distal portion. The
continuous distal portion of the balloon 142 provides a gentle surface
with which to contact vessel walls so as to avoid tearing, puncturing,
and/or otherwise damaging vessel walls. Additionally, the cooling
assembly 130 shown in FIG. 2B can have a shorter overall length than a
distally connected balloon, which may facilitate positioning the cooling
assembly 130 in relatively short vessels (e.g., a renal artery having a
length of 6 cm or less).

[0124] The cooling assembly 130 can further include an orifice 144 in
fluid communication with the expansion chamber. In one embodiment, the
orifice 144 can be defined by a distal end of a capillary tube 146
inserted into the distal end 135 of the supply lumen 132. Alternatively,
the opening at the distal end 135 of the supply lumen 132 can define an
orifice. The capillary tube 146 and/or the orifice 144 can have a
diameter less than that of the supply lumen 132 to impede the flow of
refrigerant proximate the expansion chamber, thereby increasing the
pressure drop of the refrigerant 106 entering the expansion chamber and
concentrating the refrigeration power at the cooling assembly 130. In
other embodiments, the supply lumen 132 may have a substantially constant
inner diameter (e.g., 0.008 inch (0.203 mm), 0.009 inch (0.023 mm), 0.010
inch (0.254 mm), etc.) such that the orifice 144 has a diameter at least
equal to that of the supply lumen 132. The cryotherapeutic device 120 can
then further include additional hardware (e.g., valves, flow and pressure
gauges, etc.) and/or software in the handle 125 (FIG. 1) and/or in the
console 102 (FIG. 1) to control the refrigerant 106 through the supply
lumen 132 and focus the refrigeration power toward the distal end portion
126 of the shaft 122.

[0125] The orifice 144 can be sized relative to the area and/or length of
the exhaust lumen 134 at the distal portion 126 of the shaft 122 to
provide a sufficient flow rate of refrigerant, produce a sufficient
pressure drop in the expansion chamber, and allow for sufficient venting
of the exhausted refrigerant 117 through the exhaust lumen 134. In one
embodiment, the orifice 144 can have a diameter of approximately 0.003
inch (0.076 mm) or more, such as about 0.004 inch (0.101 mm) to about
0.009 inch (0.229 mm). In various embodiments, the inner diameter and/or
cross-sectional area of the exhaust lumen 132 and the diameter and/or
cross-sectional area of the orifice 144 can have a ratio between
approximately 4:1 and 10:1. For example, the exhaust lumen 132 can have
an inner diameter between approximately 0.030 inch (0.762 mm) and
approximately 0.050 inch (1.27 mm), and the orifice 144 can have a
diameter of approximately 0.003 inch (0.0762 mm) to approximately 0.008
inch (0.203 mm; e.g., 0.004 inch (0.101 mm)). In other embodiments, the
exhaust lumen 134 and the orifice 144 can have other suitable dimensions.
In further embodiments, the shaft 122 may include additional lumens or
devices extending there through (e.g., pressure sensing lumens,
additional fluid passageways, etc.) and the ratio of the cross-sectional
dimension of the exhaust lumen 132 to the total cross-sectional dimension
occupied by the supply lumen and/or other members within the shaft 122
can be approximately 4:1 and 10:1.

[0126] The flow rate of the refrigerant 106 can also be manipulated by
changing the lengths of the supply lumen 132 and the capillary tube 146
relative to one another. For example, in certain embodiments, the
capillary tube 146 can be at most 1/3 the length of the supply lumen 132.
In various embodiments, the capillary tube 146 can have a length between
2 inches (5.08 cm) and 30 inches (76.2 cm) and the supply lumen 132 can
be sized accordingly. In other embodiments, the capillary tube 146 can be
shorter or longer relative to the supply lumen 132 and/or the capillary
tube 146 can be omitted.

[0127] The cooling assembly 130 is passed intravascularly to a target site
T in a vessel V while in the delivery configuration shown in FIG. 2A.
Referring to FIG. 2B, the cooling assembly 130 and the sheath 150 are
then moved relative to each other such that the cooling assembly 130
extends distally beyond the sheath 150. For example, the sheath 150 can
be pulled proximally and/or the cooling assembly 130 can be pushed
distally. In operation, the refrigerant 106 passes through the supply
lumen 132, through the orifice 144, and into the expansion chamber
defined by the balloon 142. As the refrigerant 106 passes through the
orifice 144, it expands into a gaseous phase, thereby inflating the
balloon and causing a significant temperature drop in the expansion
chamber. The portion of the applicator 140 contacting the tissue at the
target T can be a heat-transfer region 149 or heat-transfer zone that,
together with the refrigerant 106 in the expansion chamber, causes
therapeutically-effective, cryogenic renal-nerve modulation. Exhausted
refrigerant 117 passes in a proximal direction through the exhaust lumen
134. In various embodiments, the length of shaft 122 can be minimized to
decrease the losses (e.g., friction losses) of the refrigerant flowing
through the supply lumen 132 and through the exhaust lumen 134, thereby
enhancing the refrigeration potential and the efficiency of the cooling
assembly 130. The additional friction losses that may be caused by longer
exhaust lumens, for example, may inhibit venting of the exhausted
refrigerant 117, and thereby increase the pressure and temperature within
the balloon 142. Accordingly, the shaft 122 can be configured to have a
total overall length of less than 90 cm (e.g., 80 cm to 85 cm, 70 cm to
80 cm, etc.). In other embodiments, the shaft 122 can be longer and/or
include additional features to enhance the refrigeration power at the
cooling assembly 130.

[0128] The embodiment of the cooling assembly 130 illustrated in FIGS. 2A
and 2B fully occludes the vessel V and produces a full-circumferential
treatment at the target site T (i.e., a continuous cooled region
extending completely around the inner circumference of the vessel V in a
plane that is perpendicular or otherwise transverse relative to a
longitudinal direction of the vessel V at the target T). Fully occluding
the vessel V limits blood flow from heating the heat-transfer region 149
such that the cooling power of the refrigerant can be more efficiently
applied to the target T. Although occlusion of the renal blood vessel for
an excessive period of time can potentially cause ischemia of a kidney,
it has been found that renal blood flow can be fully occluded for a
period of time sufficient to complete cryotherapy at the target T (e.g.,
2-5 minutes). The controller 118 (FIG. 1) can be programmed to limit the
duration of refrigerant flow (e.g., 2-5 minutes) by using an electronic
or mechanical timer to control a valve. Alternatively, a timer can be
incorporated into the handle 125 (FIG. 1) or other portion of the
cryotherapeutic device 120. If present, the sensor 138 may provide
feedback to the controller 118 to regulate or control the system 100. In
some embodiments, it may be desirable for the control algorithm to be
fully automated, but in other embodiments the delivered therapy may
utilize user input. In further embodiments, the duration of refrigerant
flow can be limited by the volume of the refrigerant in the supply
container 104. As described in greater detail below, in other
embodiments, the cooling assembly 130 can be configured to partially
occlude blood flow.

[0129] In various embodiments, the sensor 138 can be a thermocouple
positioned on an outer surface of the balloon 142 and configured to
provide a real-time temperature reading of the external temperature of
the balloon 142. As such, the cryotherapeutic system 100 can be regulated
via the controller 118 (e.g., using a software control loop) such that it
ramps the cooling power output up and down based on the difference
between the real-time external balloon temperature and a predetermined
treatment temperature (e.g., -40° C., -60° C., etc.). For
example, the cooling power output can be regulated by switching valves
(e.g., the supply control valve 108 and/or the backpressure control valve
113) on and off at various stages of a cryotherapeutic treatment in
response to measured temperatures. In other embodiments, the cooling
power output can be modulated using proportional control wherein the
delivery pressure of the refrigerant 106 and/or the flow rate of the
vacuum pump 111 can be varied in response to the measured external
balloon temperature. Accordingly, the external thermocouple allows the
cryotherapeutic system 100 to compensate for variables that affect
cooling at the target site T, such as variations in artery diameter,
blood flow through the artery, and/or blood flow through other vessels in
the vicinity of the renal artery.

[0130] FIGS. 2C-2E are enlarged cross-sectional views illustrating the
distal portion 126 of the cryotherapeutic device 120 configured in
accordance with other embodiments of the present technology. Referring to
FIG. 2c, a distal portion 152 of the balloon 142 can be connected to a
distal connector 162 via thermal bonding, adhesives, and/or other
suitable attachment mechanisms. The distal connector 162 can have a
curved, bullet-like tip as shown in FIG. 2c or can be otherwise
configured to provide an atraumatic tip for navigation through the
vasculature.

[0131] The cryotherapeutic device 120 further includes a guide wire lumen
133a through which a guide wire 133b can be received to guide the distal
portion 126 of the shaft 122 through the vasculature. In the embodiment
illustrated in FIG. 2c, the guide wire lumen 133a extends completely
through the shaft 122 from the proximal opening of the shaft 122 at an
adaptor 201 (e.g., at the handle 125 shown in FIG. 1) to beyond the
distal opening of the shaft 122 in an over-the-wire (OTW) configuration,
whereas in the embodiment illustrated in FIG. 2E, the guide wire lumen
133a extends through only a portion of the shaft 122 in a rapid exchange
(RX) configuration. Although the proximal end of the guide wire lumen
133a is shown in FIG. 2E extending through the sidewall of the shaft 122
at the distal portion 126, in other embodiments, the proximal end of the
guide wire lumen 133a can be accessible anywhere between the proximal and
distal ends of the shaft 122. The guide wire lumen 133a shown in FIGS.
2C-2E, or variations thereof, may be included in various embodiments
described herein to facilitate navigation through the vasculature.
Suitable OTW and RX guide wire configurations are disclosed in U.S. Pat.
No. 545,134, filed Oct. 27, 1994, U.S. Pat. No. 5,782,760, filed May 23,
1995, U.S. Patent Publication No. 2003/0040769, filed Aug. 23, 2001, and
U.S. Patent Publication No. 2008/0171979, filed Oct. 17, 2006, each of
which is incorporated herein by reference in its entirety.

[0132]FIG. 3A illustrates cryogenically modulating renal nerves with an
embodiment of the system 100. The cryotherapeutic device 120 provides
access to the renal plexus through an intravascular path P that leads to
a respective renal artery RA. As illustrated, a section of the proximal
portion 124 of the shaft 122 is exposed externally of the patient. By
manipulating the proximal portion 124 of the shaft 122 from outside the
intravascular path P, the caregiver may advance the shaft 122 through the
tortuous intravascular path P (e.g., via the femoral artery or a radial
artery) and remotely manipulate the distal portion 126 (e.g., with an
actuator in the handle 125). For example, the shaft 122 may further
include one or more pull-wires or other guidance devices to direct the
distal portion 126 through the vasculature. Image guidance, e.g., CT,
radiographic, IVUS, OCT or another suitable guidance modality, or
combinations thereof, may be used to aid the caregiver's manipulation.
After the cooling applicator 140 is adequately positioned in the renal
artery RA or at the renal ostium, it can be expanded or otherwise
deployed using the console 102 (FIG. 1), the handle 125 (FIG. 1), and/or
another means until the applicator 140 contacts the inner wall of the
renal artery RA. The purposeful application of cooling power from the
applicator 140 is then applied to tissue to induce one or more desired
neuromodulating effects on localized regions of the renal artery and
adjacent regions of the renal plexus, which lay intimately within,
adjacent to, or in close proximity to the adventitia of the renal artery.
The purposeful application of the neuromodulating effects may achieve
neuromodulation along all or a portion of the renal plexus.

[0133] The neuromodulating effects are generally a function of, at least
in part, the temperature of the applicator 140, contact between the
applicator 140 and vessel wall, dwell time of the applicator 140 while
cooling, number of cooling cycles (e.g., one or more cooling cycles
separated by a warming period), and blood flow through the vessel.
Desired cooling effects may include cooling the applicator such that the
temperatures of target neural fibers are below a desired threshold to
achieve cryo alteration or ablation. For example, the refrigerant gas in
the applicator 140 can be cooled to a temperature of about -88° C.
to about -60° C., or in other embodiments the gas in the
applicator 140 can have a temperature of about -80° C. to about
-40° C.

[0134] In various embodiments, neuromodulating effects can occur within
100 seconds (e.g., 90 seconds, 75 seconds, 60 seconds, 30 seconds, etc.)
of applying the cooled applicator 140 to the renal artery RA or renal
ostium in one or more cooling cycles. In one embodiment, the process can
include two cooling cycles separated by a warming period, but in other
embodiments the process can have more than two cooling cycles separated
by warming periods. The cooling cycles can have the same duration or
different durations, such as approximately 10 seconds to approximately 90
seconds each. The duration(s) of the warming periods can be sufficient to
partially or completely thaw frozen matter at the cooling interface. In
several embodiments, the duration(s) of the warming periods can be from
about 5 seconds to about 90 seconds. Individual warming periods between
cooling cycles may last for the same amount of time or for different
amounts of time. The durations of the cooling and warming cycles can be
predetermined and programmed into an algorithm, or the system can include
an automatic control algorithm using a feedback loop based on the
pressure and/or temperature within and/or on the external surface of the
balloon. For example, the control algorithm can terminate a warming cycle
and initiate a cooling cycle by assessing when the frozen matter has
sufficiently thawed based on the pressure and/or temperature
measurements. Depending upon the number and length of cooling cycles, the
total procedure time from the deployment of the cooling assembly 130
(e.g., as shown in FIG. 2B) to retraction of the cooling assembly to the
delivery state (e.g., as shown in FIG. 2A) can be less than five minutes
(e.g., less than 3 minutes). When both renal arteries RA are treated, the
total procedure time from the time of deployment of the cooling assembly
130 in the first renal artery RA, to repositioning, deployment, and
retraction of the cooling assembly 130 in the second renal artery RA can
be less than 12 minutes (e.g., 10 minutes, 6 minutes, etc.). In certain
embodiments, the procedure time can be decreased by locating the
applicator 140 around a full circumference of the renal artery RA (e.g.,
along the same plane or along parallel planes spaced laterally apart) and
performing neuromodulation in a single application. In other embodiments,
the applicator 140 can be applied to less than a full circumference of
the renal artery RA and/or in more than one application.

[0135]FIG. 3B is a block diagram illustrating a method 300 of
cryogenically modulating renal nerves using the system 100 described
above with reference to FIGS. 1-3A or another suitable system in
accordance with an embodiment of the present technology described below.
Referring to FIGS. 1-3B together, the method 300 can include
intravascularly locating the cooling assembly 130 in the delivery state
(e.g., as shown in FIG. 2A) in a renal artery or renal ostium (block
305). The cryotherapeutic device 120 and/or portions thereof (e.g., the
cooling assembly 130) can be inserted into a guide catheter (e.g., the
sheath 150 shown in FIGS. 2A-2C) to facilitate intravascular delivery of
the cooling assembly 130. In certain embodiments, for example, the
cryotherapeutic device 120 can be configured to fit within an 8 Fr guide
catheter or smaller (e.g., 7 Fr, 6 Fr, etc.) to access small peripheral
vessels. As described above, an OTW or RX guide wire can also be used to
manipulate and enhance control of the shaft 122 and the cooling assembly
130.

[0136] The method 300 can further include connecting the cryotherapeutic
device 120 to the console 102 (block 310), and partially or fully
inflating an expandable member of the cooling assembly 130 (e.g., the
balloon 142) to determine whether the cooling assembly 130 is in the
correct position at the target site (blocks 315 and 320). The expandable
member can be inflated via the supply lumen 132 with refrigerant from the
supply container 104 at the console 102 and/or with other suitable fluids
(e.g., air) from a secondary fluid supply reservoir in fluid
communication the expandable member. If the cooling assembly 130 is not
in the desired location, at least some of the pressure in the expandable
member can be released (block 325). In certain embodiments, for example,
the expandable member can be fully deflated by disconnecting the
cryotherapeutic device 120 from the console 102 and using a syringe to
manually deflate the expandable member via a proximal end portion of the
shaft 122. In other embodiments, the cryotherapeutic device 120 can
remain attached to the console 102, and a syringe can be connected along
the length of the shaft 122 (e.g., a stopcock syringe) to deflate the
expandable member. In further embodiments, the controller 118 at the
console 102 can include algorithms for partially or fully deflating the
expandable member. In still further embodiments, the cooling assembly 130
can be positioned at the target site using radiopaque markers and/or
markings.

[0137] Once the cooling assembly 130 is properly located within the first
renal artery or ostium thereof, the console 102 can be manipulated to
initiate cooling at the cooling assembly 130 that modulates the renal
nerves to cause partial or full denervation of the kidney (block 330).
Cryogenic cooling can be applied for one or more cycles (e.g., for 30
second increments, 60 second increments, 90 second increments, etc.) in
one or more locations along the circumference and/or length of the first
renal artery or first renal ostium. In one particular embodiment, for
example, two 90 second cycles may be used. In various embodiments, the
expandable member can remain fully or partially inflated to maintain the
position of the cooling assembly 130 at the target site between cooling
cycles.

[0138] After renal-neuromodulation at the first renal artery, the method
300 can further include deflating the expandable member and retracting
the cooling assembly 130 into the delivery state (block 335). The
expandable member can be deflated manually by detaching the
cryotherapeutic device 120 from the console 102 and connecting a syringe
or other suitable evacuation device to the proximal end of the shaft 122.
In other embodiments, a syringe can be connected along the length of the
shaft 122 without detaching the cryotherapeutic device 120 from the
console 102, or the expandable member can be deflated automatically
(e.g., via the controller 118). In certain embodiments, the cooling
assembly 130 can be withdrawn back into the guide catheter after the
expandable member is deflated. Optionally, the cooling assembly 130 can
be removed from the guide catheter during repositioning and temporarily
stored in a sterile location (e.g., in a saline solution).

[0139] The cooling assembly 130 can then be located in a second renal
artery or second renal ostium (block 340), and the expandable member can
be expanded to confirm the position of the cooling assembly 130 (block
345). In selected embodiments, a contrast material can be delivered
distally beyond the cooling assembly 130 and fluoroscopy and/or other
suitable imaging techniques can be used to locate the second renal
artery. If necessary, the used supply container 104 in the console 102
can be refilled or removed and replaced with a new supply container
(e.g., a disposable refrigerant cartridge) to provide sufficient
refrigerant for renal-neuromodulation at the second renal artery or
second renal ostium. In embodiments where the console 102 was detached
from the cryotherapeutic device 120 during repositioning of the cooling
assembly 130, the console 102 can be reconnected to the cryotherapeutic
device 120 such that the method 300 continues by applying cryogenic
cooling to effectuate renal-neuromodulation at the second renal artery or
second renal ostium (block 350).

[0140] In other embodiments, various steps in the method 300 can be
modified, omitted, and/or additional steps may be added. For example, the
console 102 can be turned on and loaded with the supply container 104
outside the sterile field in which the cryotherapy occurs, and positioned
in a sterile bag or housing such that it can be brought into the sterile
field. If the supply container 104 must be reloaded or refilled during
cryotherapy, the console 102 can be removed from the sterile field,
reloaded, and placed back into the sterile field (e.g., in a sterile bag
or housing). In other embodiments, the empty supply container 104 can be
removed from the console 102 and deposited within a sterile bag or
housing surrounding the console 102, and a new supply container can be
attached to the console 102 within the sterile bag or housing such that
the console 102 does not leave the sterile field during treatment. In
further embodiments, the console 102 can remain outside the sterile field
and operated remotely.

[0141]FIG. 4A is an enlarged cross-sectional view of a distal portion 426
of a cryotherapeutic device 420 configured in accordance with another
embodiment of the present technology. The cryotherapeutic device 420
includes features generally similar to the features of the
cryotherapeutic device 120 described above with reference to FIGS. 1-3B.
For example, the cryotherapeutic device 420 includes the elongated shaft
122, the supply and exhaust lumens 132 and 134 extending along at least a
portion of the shaft 122, and the cooling assembly 130 at the distal
portion 426 of the shaft 102. The cooling assembly 130 includes an
expandable member, such as the balloon 142 or other suitable expandable
member, that defines at least a portion of the expansion chamber and
receives the refrigerant 106 in an at least substantially gas phase via
the orifice 144.

[0142] In the illustrated embodiment, the distal end 135 of the supply
lumen 132 is coupled to a distal portion 452 of the balloon 142 to
provide additional support and/or control for the cooling assembly 130,
and the orifice 144 is an opening positioned along the length of the
supply lumen 132 (e.g., rather than at the distal end 135 of the supply
lumen 132 or at the end of a capillary tube). The supply lumen 132 and
the distal portion 452 of the balloon 142 can be attached together using
adhesives (e.g., thermal bonds), fasteners, and/or other suitable
attachment mechanisms known in the art. In other embodiments, the supply
lumen 132 can terminate at or in the expansion chamber, and/or the
cryotherapeutic device 420 can further include a support member (not
shown) that extends from the shaft 122 to at least the distal portion 452
of the balloon 142.

[0143] As shown in FIG. 4A, the cryotherapeutic device 420 can further
include a connector 454 at the proximal portion of the balloon 142 that
can be attached over the distal portion 426 of the shaft 122 and thereby
couple the balloon 142 to the shaft 122. The connector 454 can be defined
by a proximal portion of the balloon 142 (e.g., the neck of the balloon
142) that is integral with the expandable portion as shown in FIG. 4A, or
the connector 454 can be a separate and distinct component from the
balloon 142, such as a collar or other suitable retainer. The connector
454 can be attached to the distal portion 426 of the shaft 122 using
thermal bonds, adhesives, interlocking surfaces (e.g., threads), friction
fit, snap fit, suction, and/or other suitable attachment mechanisms, or
the connector 454 can be formed integrally with the distal portion 426.

[0144] In the illustrated embodiment, the connector 454 is positioned
proximate the step 128 over the second zone 127b of the distal portion
426 of the shaft 122. As shown in FIG. 4A, the first zone 127a of the
distal portion 426 can have a first outer cross-sectional dimension or
diameter OD1 and the second zone 127b distal to the step 128 can
have a second outer cross-sectional dimension or diameter OD2 less
than the first outer cross-sectional dimension OD1. The reduction in
the outer dimension of the distal portion 426 at the step 128 forms an
inward recess relative to the first zone 127a in which at least a portion
of the connector 454 and the proximal region of the expandable portion of
the balloon 142 can sit, and thereby reduces the profile of the distal
portion 426 of the shaft 122. In certain embodiments, the step 128 can be
dimensioned such that an outer surface 455 of the first zone 127a is at
least substantially flush with an outer surface 457 of the connector 454.
Accordingly, the outer diameter OD2 of the second zone 127b can be
equivalent to the outer diameter OD1 of the first zone 127a less
twice the thickness of the connector 454. In other embodiments, the outer
diameter OD2 of the second zone 127b can be greater than or less
than twice the thickness of the connector 454.

[0145] In selected embodiments, the connector 454 is non-expandable such
that it remains within the recess and/or substantially flush with the
outer surface 455 of the first zone 127a when the cooling assembly 130
moves to the deployed state (e.g., as shown in FIG. 4A). In other
embodiments, the connector 454 may be expandable and increase in
cross-sectional area as the cooling assembly 130 moves to the deployed
state.

[0146] In the embodiment shown in FIG. 4A, the cross-sectional area of the
exhaust lumen (e.g., defined by the inner surface(s) of the shaft 122)
also decreases at the transition between the first zone 127a and the
second zone 127b such that the distal portion 426 of the shaft 122 has a
first inner cross-sectional dimension or diameter ID1 at the first
zone 127a and a lesser second inner cross-sectional dimension or diameter
ID2 at the second zone 127b. To avoid a build up of pressure in the
expansion chamber that may be caused by insufficient venting through the
necked-down exhaust lumen 134, the second zone 127b can be positioned
only at the distal-most end of the shaft 122 proximate the expansion
chamber where the density of the exhausted refrigerant 117 is the
highest. For example, the second zone 127b can have a length of less than
4 cm (e.g., 2 cm, 1 cm, etc.). The exhausted refrigerant 117 also vents
adequately through the smaller inner diameter ID2 of the second zone
127b without undue restriction because the length of the second zone 127b
along the longitudinal axis of the shaft 122 can be relatively short. For
example, the length of the second zone 127b can be minimized to
sufficiently accommodate the connector 454. Accordingly, the smaller
exhaust lumen 134 at the second zone 127b can transport primarily high
density exhausted refrigerant 117 and can expel the exhausted refrigerant
117 into the larger exhaust lumen 134 at the first zone 127a as the
exhausted refrigerant 117 decreases in density, thereby facilitating
adequate venting through the smaller second inner diameter ID2 of
the second zone 127b.

[0147] In operation, the inwardly recessed second zone 127b can reduce the
profile of the distal portion 426 of the shaft 122 and/or provide a
substantially smooth transition from the shaft 122 to the connector 454
without jeopardizing the venting characteristics of the exhaust lumen
134. The low-profile distal portion 426 of the shaft 122 can also
facilitate the delivery of a fluidic contrast material between the shaft
122 and the sheath 150 from the proximal portion 124 (FIG. 1) of the
shaft 122 to the distal portion 426 and around the cooling assembly 130
in the delivery state (e.g., as shown in FIG. 2A) to image and locate
(e.g., using fluoroscopy) a target in the vasculature. As shown in FIG.
4A, for example, the recessed second zone 127b provides one or more
passageways or channels C around the distal portion 426 of the shaft 122
that are large enough to deliver contrast material distally beyond the
cooling assembly 130 without being blocked by a protruding connector or
balloon. In certain embodiments, a sufficient channel C for the contrast
material can be formed when the difference between the first outer
diameter OD1 and the second outer diameter OD2 of the
corresponding first and second zones 127a and 127b is less than 0.01 inch
(0.254 mm). In other embodiments, the difference between the outer
dimensions OD1 and OD2 of the first and second zones 127a and
127b may be greater or smaller. When used during renal-neuromodulation, a
first renal artery can be located by delivering contrast material
distally beyond the cooling assembly 130 in the delivery state via the
channel C. After renal-neuromodulation at the first renal artery, the
cooling assembly 130 can be retracted back from the deployed state to the
delivery state wherein additional contrast material can be delivered
distally beyond the cooling assembly 130 via the channel C to locate a
second renal artery.

[0148] In other embodiments, the distal portion 426 of the shaft 122 does
not include the stepped-down exhaust lumen 134 shown in FIG. 4A and,
instead, may have a substantially uniform cross-sectional dimension. Such
an exhaust lumen may relatively easily accommodate a guide wire lumen
(e.g., as shown in FIGS. 2C-2E) through which a guide wire can be
extended to locate the cooling assembly 130 at the target site T in the
vessel V. In this embodiment, contrast material for imaging target sites
(e.g., two renal arteries) can be delivered distally via the guide wire
lumen after the guide wire has been retracted.

[0149] FIG. 4B is an enlarged cross-sectional view of a distal portion 456
of a cryotherapeutic device 460 configured in accordance with another
embodiment of the present technology. The cryotherapeutic device 460
includes features generally similar to the features of the
cryotherapeutic device 420 described above with reference to FIG. 4A. For
example, the distal portion 456 of the shaft 122 has the step 128 that
demarcates the first zone 127a from the smaller second zone 127b.
However, in the embodiment shown in FIG. 4B, the second zone 127b is
defined by a separate tube 459 that protrudes from the shaft 122. The
tube 459 decreases the cross-sectional area of the exhaust lumen 134 at
the second zone 127b similar to the inwardly stepped portion of the shaft
122 shown in FIG. 4A.

[0150] As shown in FIG. 4B, the cryotherapeutic device 460 can further
include a proximal connector 458 that attaches the balloon 142 to the
distal portion 456 of the shaft 122. Unlike the connector 456 of FIG. 4A
that sits substantially within the recess formed by the step 128, the
proximal connector 458 shown in FIG. 4B extends over the second zone 127b
onto the outer surface 455 of the first zone 127a. By extending the
proximal connector 456 over the first zone 127a, a larger surface area is
made available for attaching the balloon 142 to the distal portion 456 of
the shaft 122. Accordingly, the length of the second zone 127b can be
reduced to facilitate adequate venting of the refrigerant 117 through the
necked-down exhaust lumen 134 (e.g., as shown in FIGS. 4A and 4B).

[0151] In certain embodiments, the proximal connector 458 is
non-expandable such that it maintains a substantially low profile against
the outer surface 455 of the first zone 127a in both the deployed and
delivery states. This can reduce or prevent the proximal connector 458
from catching on the sheath 150 as it is retracted from the deployed to
the delivery configuration. In other embodiments, at least a portion of
the proximal connector 458 can be expandable, but configured to maintain
the low profile of the distal portion 456 while the cooling assembly 130
is in the delivery state. Accordingly, the cryotherapeutic device 460
with the extended proximal connector 458 can provide a substantially low
profile for intravascularly delivering the cooling assembly 130 at a
target site within a small, peripheral vessel (e.g., a renal artery)
and/or can provide one or more channels C through which a fluidic
contrast material can be delivered distally beyond the cooling assembly
130.

[0152] As further shown in FIG. 4B, the cryotherapeutic device 460 also
includes a distal connector 462 that retains the distal portion 452 of
the balloon 142 and a support member 433 extending through the balloon
142 that braces the balloon 142 in both the delivery and deployed states.
The distal connector 462 can also be attached to (e.g., by thermal
bonding) or formed integrally with an atraumatic tip 464 that extends
distally therefrom. The atraumatic tip 464 can extend approximately 0.5
cm to 5 cm (e.g., approximately 1-2 cm) from the distal connector 462 and
have an outer diameter between approximately 0.010 inch (0.254 mm) to
approximately 0.050 inch (1.27 mm). In one embodiment, for example, the
atraumatic tip 464 can have a length of approximately 2 cm and an outer
diameter of at least 0.035 inch (0.889 mm; e.g., 0.038 inch (0.965 mm)).
In other embodiments, the atraumatic tip 464 can have other suitable
lengths and/or outer diameters. The atraumatic tip 464 can serve as a
fixed guide to facilitate navigation through the vasculature. In several
embodiments, the angle and/or rotational orientation of the atraumatic
tip 464 can be adjusted by a control wire 467 (e.g., a pull-wire) that
extends through at least a portion of the shaft 122. A user can
manipulate the control wire 467 to tortionally deflect or otherwise move
the atraumatic tip 464 to steer the distal portion 456 of the shaft 122
to the target site T. In other embodiments, the atraumatic tip 464 can be
defined by a distal end portion of a guide wire (e.g., the guide wire
133b shown in FIG. 2c) that extends through the shaft 122 and beyond the
distal connector 462.

[0153] The atraumatic tip 464 can be made from substantially smooth and
flexible materials or structures such that it can gently contact and
deflect off of vessel walls as the cryotherapeutic device 460 navigates
the vasculature, and therefore avoids perforation and/or other trauma to
the vessels through which it navigates. For example, the atraumatic tip
464 can be made from a flexible coil (e.g., a platinum coil) over a core
or wire (e.g., a stainless steel wire). In various embodiments, the wire
can be configured to gradually taper from a proximal portion 469a of the
atraumatic tip 464 to a distal portion 469b of the atraumatic tip 464. A
tapered wire, for example, can be generally round at the proximal portion
469a having an outer diameter between approximately 0.005 inch (0.127 mm)
and 0.015 inch (0.381 mm; e.g., 0.009 inch (0.229 mm)) and can flatten
toward the distal portion 469b to a thickness between approximately 0.001
inch (0.025 mm) and approximately 0.005 inch (0.127 mm; e.g., 0.003 inch
(0.076 mm)). In selected embodiments, the wire is substantially flat by
about 1/3 to 1/2 of the length of the atraumatic tip 464 from the
proximal terminus. In other embodiments, the atraumatic tip 464 can have
a tapered or non-tapered generally circular cross-section throughout. In
several embodiments, at least a portion of the atraumatic tip 464 (e.g.,
a coil wrapped around the wire) can be made from platinum and/or other
radiopaque materials (e.g., a platinum/iridium alloy) that can facilitate
navigation of the cryotherapeutic device 460 through the vasculature
using imaging techniques known in the art. In certain aspects of the
technology, the balloon 142 can also include radiopaque markers and/or
radiopaque markings (e.g., made with radiopaque ink) at both its proximal
and distal end portions to further facilitate navigation and deployment.
In other embodiments, the atraumatic tip 464 can be made from other
deflectable and gentle materials and structures, such as a polymer
material (e.g., Pebax® polymer, nylon, etc.), a polymer material over
a metallic wire (e.g., a stainless steel wire), and/or other suitable
materials.

[0154] In the embodiment illustrated in FIG. 4B, the atraumatic tip 464 is
shaped and/or otherwise formed into a curve or angled portion. When the
atraumatic tip 464 is made from a shapeable material (e.g., stainless
steel, platinum, etc.), the atraumatic tip 464 can be formed and/or
reformed into the desired curvature. In other embodiments, the atraumatic
tip 464 can be pre-formed from a non-shapeable material such that it has
a non-adjustable, set curve. The curve in the atraumatic tip 464 can
further aid in navigation of the vasculature. For example, the curve can
aid in keeping the cooling assembly 130 within a desired vessel (e.g., a
renal artery) and avoiding side branches thereof.

Pressure Monitoring in Cryotherapeutic Systems

[0155]FIG. 5A is a partially schematic view of a cryotherapeutic system
500 configured in accordance with another embodiment of the present
technology, and FIG. 5B is an enlarged cross-sectional view of a distal
end portion of the system 500 of FIG. 5A. The cryotherapeutic system 500
can include features generally similar to the features of the
cryotherapeutic system 100 described above with reference to FIGS. 1-3B.
Referring to FIG. 5A, for example, the cryotherapeutic system 500 can
include a cryotherapeutic device 520 and a console 502. The console 502
can include a refrigerant supply container 504 and a supply control valve
508 that are coupled to a supply line 510 configured to transport the
refrigerant 506 to the cryotherapeutic device 520. The console 502 can
also optionally include a pump 511 and/or a backpressure control valve
513 that are coupled to an exhaust line 515 configured to receive
evaporated refrigerant 517 from the cryotherapeutic device 520. A
controller 518 can be operably coupled to the supply control valve 508
and/or the backpressure control valve 513 to regulate refrigerant flow
through the cryotherapeutic device 520. In the illustrated embodiment,
the cryotherapeutic device 520 includes a shaft 522, a handle 525 at a
proximal region of a proximal portion 524 of the shaft 522, and a distal
portion 526 having a cooling assembly 530 at a distal end region of a
distal portion 526 of the shaft 522.

[0156] As further shown in FIG. 5A, the console 502 can also include a
pressure transducer or sensor 570 (e.g., a PX209-100G5V pressure
transducer made by Omega Engineering of Stamford, Conn.) coupled to a
pressure line 571 to monitor pressure within a portion of the cooling
assembly 530 (e.g., an expansion chamber) during cryotherapy. In various
embodiments, the pressure sensor 570 can be coupled to the controller 518
to serve as a feedback mechanism that controls the supply control valve
508 and/or the backpressure control valve 513, and thereby regulates
refrigerant flow to and/or from the cooling assembly 530 in response to a
pressure sensed at the cooling assembly 530. For example, the pressure
sensor 570 can be configured to indicate a pressure above a predetermined
threshold (e.g., within a range of a burst pressure of the expansion
chamber). In response, the controller 518 can decrease or terminate
refrigerant flow by at least partially closing the supply control valve
508 and/or increasing refrigerant flow from the cooling assembly 530 by
decreasing the backpressure in the exhaust line 515 (e.g., using the
vacuum pump 511). In other embodiments, the pressure sensor 570 can be
coupled directly to the supply control valve 508 and/or the backpressure
control valve 513 to automatically regulate the valves 508 and 513 on
and/or off in response to a sensed pressure. In several embodiments, the
cryotherapeutic system 500 can be configured to verify that the pressure
sensor 570 is calibrated properly before cryotherapy. For example, the
system 500 can automatically check the functionality of the pressure
sensor 570 as the system 500 powers on by comparing a pressure reading
from the pressure sensor 570 with the ambient pressure.

[0157] Referring now to FIG. 5B, the distal region of the cryotherapeutic
device 520 can include features generally similar to the features of the
cryotherapeutic device 120 described above with reference to FIGS. 2A-2E.
For example, the cryotherapeutic device 520 includes the supply lumen 132
coupled to the supply line 510 (FIG. 5A), the exhaust lumen 134 coupled
to the exhaust line 515 (FIG. 5A), and the applicator 140 including the
balloon 142 or other type of expandable member that defines the expansion
chamber.

[0158] As shown in FIG. 5B, the cryotherapeutic device 520 can further
include a pressure monitoring lumen 572 coupled to the pressure sensor
570 (FIG. 5A) via the pressure line 571 (FIG. 5A). The pressure
monitoring lumen 572 can extend through the shaft 522 and have a distal
opening 574 in fluid communication with the expansion chamber (e.g.,
defined by the balloon 142). The dimensions (e.g., cross-sectional area,
inner diameter, and/or outer diameter) of the pressure monitoring lumen
572 can be large enough to sense a pressure reading within the expansion
chamber with substantial accuracy, but small enough to reduce or prevent
interference with the outflow of refrigerant through the exhaust lumen
134. For example, the supply lumen 132 and the pressure monitoring lumen
572 together can have a first cross-sectional dimension (e.g., a first
cross-sectional area) and the exhaust lumen 134 can have a second
cross-sectional dimension (e.g., a second cross-sectional area) such that
the ratio of the second cross-sectional dimension to the first
cross-sectional dimension is between 4:1 and 10:1. In certain
embodiments, the pressure monitoring lumen 572 can have an inner diameter
of no more than 0.03 inch (0.762 mm; e.g., 0.015 inch (0.381 mm), 0.010
inch (0.762 mm), etc.) and an outer diameter of no more than 0.060 inch
(1.52 mm; e.g., 0.02 inch (0.508 mm), 0.015 inch (0.381 mm), etc.), and
the exhaust lumen 134 can be sized accordingly. In the embodiment
illustrated in FIG. 5B, the pressure monitoring lumen 572 terminates in
the shaft 522 before the outer diameter necks down at the second zone
127b of the distal portion 520. This configuration may be used in
embodiments where the inner diameter of the shaft 522 necks down (e.g.,
as shown in FIGS. 4A and 4B) so as not to restrict the venting of the
expanded refrigerant 517 at the smaller second zone 127b. In other
embodiments, the opening 574 of the pressure monitoring lumen 572 can be
at or in the balloon 542.

[0159] The pressure monitoring lumen 572 can also have a length sufficient
to intravascularly locate the opening 574 along with the cooling assembly
530 at the target site T (e.g., a renal artery or renal ostium via a
femoral artery or a radial artery). For example, the pressure monitoring
lumen 572 can have a length equivalent to the full length of the shaft
522 (e.g., at least 48 inches (122 cm)). In other embodiments, the
pressure monitoring lumen 572 can have other suitable different lengths
and/or dimensions. For example, the pressure monitoring lumen 572 can
have a first length and the pressure line 571 attached thereto can have a
second length (e.g., 48 inches (122 cm), 30 inches (76 cm), 12 inches (30
cm), etc.) to extend the pressure monitoring lumen 572 to the pressure
sensor 570, thereby allowing the console 502 to be positioned in a
desired location (e.g., on a table) during cryotherapeutic treatments.

[0160] During cryotherapeutic treatments, the pressure monitoring lumen
572 and the pressure sensor 570 (FIG. 5A) may be configured to provide a
signal indicating a change in pressure within the expansion chamber. For
example, the pressure sensor 570 can be configured to indicate a
threshold pressure below the rupture pressure of the balloon 142 to
reduce the likelihood that the balloon 142 bursts during cryotherapy. The
balloon 142 may have a burst pressure dependent at least in part on the
material from which the balloon 142 is made. Compliant materials (e.g.,
polyurethane), for example, typically have lower burst pressures (e.g.,
80 psi, 100 psi, 200 psi, etc.) than non-compliant materials (e.g.,
nylon) that can have burst pressures of 300 psi or higher. The pressure
sensor 570 can be configured to monitor a threshold pressure, which may
be equal to a pressure value below the burst pressure that provides an
adequate response time to react to the change in pressure before the
balloon 142 ruptures. In other embodiments, the pressure sensor 570 can
be configured to indicate when the balloon 142 operates outside its
desired operating pressure (e.g., 20-60 psi).

[0161] The time delay between the pressure at the opening 574 of the
pressure monitoring lumen 572 at the expansion chamber and the pressure
reading at the pressure sensor 570 may depend on the volume of the
pressure monitoring lumen 572. As such, the pressure monitoring lumen 572
can have a volume that has a response time sufficient to adequately
respond to the change in pressure in the expansion chamber (e.g., before
rupture of the balloon 142). In certain embodiments, for example, the
pressure sensor 570 has a response time of less than 1.5 seconds, such as
a response time of less than 1 second, 0.2 second, 0.1 second, or 15
milliseconds. To enhance the accuracy of the pressure reading and
decrease the response time of the pressure sensor 570, the length of the
pressure monitoring lumen 572 can be shortened and significant increases
in volume in the pressure monitoring lumen 572 before connecting to the
pressure sensor 570 can be reduced. For example, the pressure monitoring
lumen 572 can be coupled to the pressure line 571 at the proximal portion
524 (FIG. 5A) of the shaft 522 (e.g., at the handle 525), and the
pressure line 571 can have a cross-sectional area similar to that of the
pressure monitoring lumen 572. In other embodiments, the pressure
monitoring lumen 572 can be coupled to the pressure sensor 570 at the
handle 525 (e.g., omitting the pressure line 571) to shorten the total
length of the pressure tube to the pressure sensor 570, and electrical
wires can be coupled to the pressure sensor 570 to carry a signal to the
console 502.

[0162] Referring to FIGS. 5A and 5B together, in certain embodiments, the
pressure line 571 and/or the pressure monitoring lumen 572 can be coupled
to the pressure sensor 570 using a fitting or adaptor 576 (e.g., a quick
connect adapter). In the embodiment illustrated in FIG. 5A, for example,
the adaptor 576 includes an internal reservoir or channel 578 that
fluidly connects the pressure line 571 with the pressure sensor 570. The
channel 578 can have a substantially small volume so as not to disrupt
the pressure differential from the pressure line 571 to the pressure
sensor 570 and enhance the accuracy of the pressure measurement. For
example, in one embodiment, the channel 578 has an internal volume of no
more than 0.1 cc. In other embodiments, the channel 578 can have a larger
internal volume. In further embodiments, the adaptor 576 can couple the
pressure monitoring lumen 572 to the pressure line 571 at the handle 525
or other position proximate the proximal portion 524 of the shaft 522.
The adaptor 576, therefore, allows the pressure monitoring lumen 572
and/or the pressure line 571 to be detached from the pressure transducer
570 after a cryotherapeutic treatment such that the pressure monitoring
lumen 572 can be discarded and the pressure transducer 570 can be stored
(e.g., along with the handle 525 and/or the console 502) for subsequent
cryotherapy treatments without disrupting the accuracy of the pressure
reading at the pressure sensor 570.

[0163] Referring back to FIG. 5B, in various other embodiments, the
cryotherapeutic device 520 can further include an additional gas supply
lumen 579 coupled to the supply container 504 (FIG. 5A) or other gas
supply reservoir to deliver additional gas to the expansion chamber and
thereby modulate the temperature of the applicator 140. For example, the
gas supply lumen 579 can deliver the refrigerant 506 (e.g., nitrous
oxide) and/or other pressurized or non-pressurized gas (e.g., air) into
the balloon 142 before or during delivery of the refrigerant 506 via the
orifice 144 to increase the pressure within the balloon 142 (e.g., from
approximately 5 psi to approximately 60 psi). The additional gas in the
balloon 142 decreases the pressure drop of the refrigerant 506 in the
expansion chamber, and thereby increases the temperature within the
balloon 142. As such, the gas supply lumen 579 can be used to initiate,
restrict, and/or suspend the inflow of additional gas to the expansion
chamber (e.g., using a valve) and regulate the temperature of the balloon
142 without requiring complex components in the console 502 (e.g., a
pressure regulator, a sub-cooler, etc.) to change the pressure drop
within the balloon 142. Additionally, when the gas supply lumen 579 is
coupled to a separate gas reservoir (e.g., an air supply), the gas supply
lumen 579 can be used to deliver a gas into the balloon 142 before
delivering the refrigerant 506 into the balloon 142 to monitor the
position of the applicator 140 at the target site T.

[0164] In further embodiments, a pressure regulator (not shown; e.g., a
pressure relief valve) can be added to the exhaust lumen 134 to trap the
evaporated refrigerant 517 from exiting the balloon 142 and/or in the
exhaust lumen 134 until the pressure within the balloon 142 is at a
predetermined value (e.g., as sensed using the pressure monitoring lumen
572). In still further embodiments, the cryotherapeutic device 520 can
include both a pressure regulator for the exhaust lumen 134 and the gas
supply lumen 579 such that the pressure within the balloon 142 can be
modulated during cryotherapeutic treatment.

Pre-Cooling in Cryotherapeutic Systems

[0165] In cryogenic renal nerve modulation, the volume of refrigerant
available for cooling can be limited. Accordingly, it can be useful to
increase the cooling capacity of a refrigerant. Pre-cooling the
refrigerant before expanding the refrigerant in a cooling assembly is one
example of a process that can increase the cooling capacity of a
refrigerant. Even when cooling occurs primarily through phase change,
using colder refrigerant before the phase change can increase the amount
of cooling. Moreover, if a supply tube is in thermal communication with
an exhaust tube, decreasing the temperature of refrigerant in the supply
tube can cool refrigerant exhaust in the exhaust tube, which can reduce
back pressure in an associated cooling assembly and thereby further
increase cooling at the associated cooling assembly. Pre-cooling can
reduce the volume of refrigerant needed for cryogenic renal nerve
modulation, which can allow smaller and more flexible shafts to be used
within the vasculature. Pre-cooling also can mitigate reductions in
cooling capacity associated with other components of a cryotherapeutic
system, such as thermally-insulative members within an applicator and
in-line solenoid valves that release heat during operation.

[0166] Pressurized refrigerant used in cryogenic renal nerve modulation
typically is supplied outside the vasculature at room temperature (e.g.,
from a room-temperature dewar). As the pressurized refrigerant travels
along a supply tube within the vasculature, it can increase in
temperature via heat transfer with warm blood and tissue. For example, as
pressurized refrigerant supplied at about room temperature (e.g., about
23° C.) passes through the vasculature at body temperature (e.g.,
about 37° C.), the temperature of the pressurized refrigerant can
increase to about 25° C. to 37° C. before reaching a
cooling assembly. Cryotherapeutic devices configured in accordance with
several embodiments of the present technology can include a pre-cooling
assembly configured to cool pressurized refrigerant before the
pressurized refrigerant expands in an associated cooling assembly. For
example, pressurized refrigerant can be cooled to have a temperature just
before expansion in an associated cooling assembly that is less than body
temperature (e.g., less than about 20° C. or less than about
10° C.). Such pre-cooling assemblies can be configured to be
outside the vasculature and/or to utilize the same refrigerant supply as
an associated cooling assembly. In several embodiments configured in
accordance with the present technology, pre-cooling can be useful to
maintain refrigerant in liquid form until it reaches a cooling assembly
where cryogenic cooling is desired. For example, evaporation associated
with warming of refrigerant passing through portions of a cryotherapeutic
device proximal to a cooling assembly can be reduced. In this section,
the terms "proximal" and "distal" can reference a position relative to a
pressurized refrigerant source. For example, proximal can refer to a
position closer to a pressurized refrigerant source, and distal can refer
to a position farther from a pressurized refrigerant source.

[0167] FIGS. 6A-6B illustrate a portion of a cryotherapeutic device 600
including a pre-cooling assembly 602, an elongated shaft 604 defining an
exhaust passage, and a hub 606 between the pre-cooling assembly and the
shaft. The pre-cooling assembly 602 includes a flexible tubular member
608 extending between the hub 606 and an adapter 610 configured to
connect to a pressurized-refrigerant source (not shown). The hub 606 can
include a primary connector 612 attached to the shaft 604, an exhaust
portal 614 venting to the atmosphere, a first branch 616 attached to the
tubular member 608, and a second branch 618 attached to a control-wire
conduit 620. In several embodiments, the hub 606 can include one or more
additional branches, such as a branch including a tube fluidly connected
to a proximal syringe adapter (e.g., a proximal syringe adapter including
a diaphragm configured to be punctured with a needle of a syringe). Such
a structure can be useful, for example, to introduce contrast agent in
the vicinity of a cooling assembly within the vasculature and/or to
introduce filler material into a filler lumen of a cooling assembly
within the vasculature. Filler materials are discussed in greater detail
below.

[0168] With reference again to FIGS. 6A-6B, two control wires 621 (FIG.
6B) can extend from the control-wire conduit 620, through the hub 606,
and into the shaft 604. The hub 606 can define a generally straight
primary-exhaust flow path from the shaft 604 to the atmosphere through
the exhaust portal 614. The tubular member 608 includes a tubular
proximal portion 622 at the adapter 610 and a tubular distal portion 624
at the first branch 616. As most clearly shown in FIG. 6B, the tubular
proximal portion 622 can include a first plug 626 and a second plug 628,
and the adapter 610 can include an opening 630 proximate the second plug
628. The adapter 610 can include a variety of suitable structures for
connection to a pressurized-refrigerant source, such as a threaded
fitting, a compression fitting, or a barbed fitting.

[0169] In the embodiment shown in FIG. 6B, the device 600 includes a
primary-supply tube 632 defining a primary-supply lumen, and the
pre-cooling assembly 602 includes a pre-cooling supply tube 634 defining
a pre-cooling supply lumen. The primary-supply tube 632 and the
pre-cooling supply tube 634 can include a primary-supply proximal opening
636 and a pre-cooling supply proximal opening 638, respectively, at the
second plug 628. The primary-supply proximal opening 636 and the
pre-cooling supply proximal opening 638 fluidly connect the
primary-supply tube 632 and the pre-cooling supply tube 634,
respectively, to a passage defined by the opening 630. From the second
plug 628, the primary-supply tube 632 and the pre-cooling supply tube 634
extend through the tubular proximal portion 622 and through the first
plug 626. The tubular distal portion 624 defines a pre-cooling expansion
chamber extending from the first plug 626 to the primary exhaust flow
path. The pre-cooling supply tube 634 extends slightly past the first
plug 626 and terminates at a pre-cooling distal opening 640 within the
pre-cooling expansion chamber. The pre-cooling expansion chamber is
accordingly in fluid connection with a flow of refrigerant through the
pre-cooling supply tube 634 such that a pre-cooling exhaust flow path
extends from the pre-cooling distal opening 640 to the primary exhaust
flow path. The primary-supply tube 632 extends through the pre-cooling
expansion chamber, through the hub 606 and into the shaft 604. The
portion of the primary-supply tube 632 extending from primary-supply
proximal opening 636 to the shaft is a first portion of the
primary-supply tube 632. A second portion (not shown) of the
primary-supply tube 632 is proximate a cooling assembly (not shown)
configured to be within the vasculature.

[0170] Expanding pressurized refrigerant into the pre-cooling expansion
chamber from the pre-cooling supply tube 634 can cool the pre-cooling
expansion chamber and thereby cool the primary-supply tube 632 and liquid
refrigerant within the primary-supply tube. If pre-cooling is performed
distant from an entry point into the vasculature (e.g., if pressurized
refrigerant is cooled in a console before being transported to an entry
point into the vasculature), heat from the atmosphere can cause
undesirable warming of the pre-cooled pressurized refrigerant.
Positioning the pre-cooling expansion chamber proximate the hub can
reduce such undesirable warming. A pre-cooling assembly configured in
accordance with several embodiments of the present technology can have a
length sufficient to allow heat-transfer between expanded refrigerant
within a pre-cooling expansion chamber and pressurized refrigerant within
a portion of a primary-supply tube within the pre-cooling expansion
chamber. For example, a pre-cooling chamber configured in accordance with
several embodiments of the present technology can have a length greater
than about 10 cm, such as greater than about 15 cm, or greater than about
25 cm. A pre-cooling chamber configured in accordance with several
embodiments of the present technology has a length from about 20 cm to
about 30 cm.

[0171] After cooling the primary-supply tube 632, refrigerant from the
pre-cooling expansion chamber can join a flow of refrigerant from the
exhaust passage and vent out the exhaust portal 614 to the atmosphere.
FIG. 6B shows a first arrow 642 indicating a flow direction of
refrigerant through the exhaust portal 614 and a second arrow 644
indicating a flow direction of refrigerant through the pre-cooling
expansion chamber. The flow direction of refrigerant through the exhaust
portal 614 is generally aligned with the exhaust passage. In contrast,
the flow direction of refrigerant through the pre-cooling expansion
chamber is not aligned with the exhaust passage or the flow direction of
refrigerant through the exhaust portal 614.

[0172]FIG. 7 illustrates a portion of a cryotherapeutic device 700
similar to the cryotherapeutic device 600 of FIGS. 6A-6B, except that the
device 700 has a pre-cooling expansion chamber fluidly separate from the
exhaust passage. The cryotherapeutic device 700, for example, includes a
pre-cooling assembly 702 including a valve 704 and a third plug 706
fluidly separating the pre-cooling expansion chamber from internal
portions of the shaft 604 and the hub 606. The primary-supply tube 632
extends through the third plug 706 and into the shaft 604.

[0173] An arrow 708 indicates a flow direction of refrigerant through the
pre-cooling expansion chamber when the valve 704 is open. When the valve
704 is closed, pressure within the pre-cooling expansion chamber can
increase until it equilibrates with the pre-cooling supply tube 634,
thereby causing flow through the pre-cooling supply tube to stop. In this
way, opening and closing the valve 704 can turn pre-cooling on or off.
Partially opening the valve 704 can regulate pressure within the
pre-cooling expansion chamber and thereby regulate refrigerant flow
through the pre-cooling supply tube 634 and an associated pre-cooling
temperature. For example, an actuator 710 can be operably connected to
the valve 704 and be configured to receive a signal from a processor 712.
The processor 712 can be configured to receive a signal from a user
interface 714 and/or a sensor 716 to direct the actuator 710 to open or
close the valve fully or incrementally. The sensor 716, for example, can
be a temperature sensor of an associated cooling assembly. In one
embodiment, the temperature sensor can send a signal to the processor 712
causing the valve 704 to (a) open and pre-cooling to increase if a
detected temperature of the cooling assembly or tissue proximate the
cooling assembly is higher than a desired value, or to (b) close and
pre-cooling to decrease if a detected temperature of the cooling assembly
or tissue proximate the cooling assembly is lower than a desired value.

[0174] FIGS. 8A-8B illustrate a portion of a cryotherapeutic device 800
with a pre-cooler 802 configured in accordance with another embodiment of
the present technology. Accessing an internal portion of the tubular
member 608 to form the first plug 626 of the pre-cooling assembly 602
(FIGS. 6A-6B) can be challenging. Instead of the first plug 626 and the
pre-cooling supply tube 634 (FIG. 6B), the pre-cooler 802 can include a
flow separator attached to a primary-supply tube. For example, the
pre-cooler 802 can include a flow separator 804 attached to a
primary-supply tube 806 and a container 808 having a container proximal
portion 810 and a container distal portion 812. In this embodiment, the
flow separator 804 divides the container 802 into the container proximal
portion 810 and the container distal portion 812. The container proximal
portion 810 defines a proximal chamber or a combined supply lumen between
the opening 630 and the flow separator 804 and the container distal
portion 812 defines a pre-cooling expansion chamber. As most clearly
shown in FIG. 8B, the flow separator 804 defines a primary passage 814
fluidly connected to the primary-supply tube 806 and a pre-cooling
passage 816 along a periphery of the flow separator 804.

[0175] Referring still to FIG. 8B, the pre-cooling passage 816 is sized to
cause a pressure drop sufficient to expand refrigerant and cool the
pre-cooling expansion chamber. The flow separator 804 includes a tubular
segment 818 and a flow-separator plug 820. The flow-separator plug 820 is
positioned between an outer surface of the primary-supply tube 806 and an
inner surface of the container 808. The tubular segment 818 can be
selected to have an outer cross-sectional dimension (e.g., diameter)
slightly smaller than an inner cross-sectional dimension (e.g., diameter)
of the container 808. The flow-separator plug 820 can include, for
example, an adhesive material configured to bond to the outer surface of
the primary-supply tube 806 and the inner surface of the container 808.

[0176] In one embodiment, the flow separator 804 floats in the container
808 (i.e., it is not fixed within the container 808) such that the
pre-cooling passage 816 is an annular space between the flow separator
804 and an inner surface of the container 808. In other embodiments, flow
separators can have different configurations. For example, a flow
separator can be fixed to the container and a pre-cooling passage can
extend through the flow separator around only a portion of the periphery
of the flow separator, such as a curved portion. In still other
embodiments, the flow separator can be attached to the container around
generally its entire circumference and the flow separator can include an
opening spaced inwardly apart from the periphery of the flow separator.
For example, a flow separator can include an internal opening configured
to expand refrigerant into the pre-cooling expansion chamber.

[0177] FIGS. 9A-9B illustrate a portion of a cryotherapeutic device 900
similar to the cryotherapeutic device 800 of FIGS. 8A-8B, except having
different flow-separator and primary-supply tube configurations. The
cryotherapeutic device 900 includes a primary supply tube 902 and a
pre-cooler 904 including a flow separator 906 attached to the
primary-supply tube 902. The pre-cooler 904 can also include a container
908 having a container proximal portion 910 and a container distal
portion 912 on opposite sides of the flow separator 906. In this
embodiment, the flow separator 906 does not include a tubular segment and
can be constructed, for example, from a cylindrical block of material
(e.g., rubber, polymer, metal, or another material) having a hole through
which the primary-supply tube 902 can be threaded or otherwise attached.
As most clearly shown in FIG. 9B, the flow separator 906 can define a
pre-cooling passage 914 along a periphery of the flow separator 906. The
primary-supply tube 902 can extend through the flow separator 906 and can
be attached to an inner surface of the container proximal portion 910
proximate the opening 630. Attaching the primary-supply tube 906 to an
accessible portion of the container proximal portion 910 can be useful to
prevent undesirable longitudinal movement of the flow separator 906 and
the primary-supply tube 902 when the proximal chamber is at high
pressure.

[0178] A pre-cooling assembly configured in accordance with several
embodiments of the present technology can be arranged in a compact
configuration. For example, at least a portion of such a pre-cooling
assembly can be within a handle of a cryotherapeutic device. FIG. 10
illustrates a portion of a cryotherapeutic device 1000 including a
pre-cooling assembly 1002 and a hub 1004 within a handle 1006. The
pre-cooling assembly 1002 includes a flexible tubular member 1008
extending from the hub 1004, through a bottom portion 1010 of the handle
1008, and to an adapter 1012 configured to connect to a
pressurized-refrigerant source (not shown). The hub 1004 can include an
elongated exhaust portal 1014 extending through the bottom portion 1010,
and a control-wire conduit 1016 can extend from the hub 1004 through the
bottom portion 1010. In one embodiment, the tubular member 1008 is coiled
around the exhaust portal 1014. The handle 1006 also can be insulated to
prevent heat loss to the atmosphere and improve pre-cooling efficiency.

[0179]FIG. 11 illustrates a portion of a cryotherapeutic device 1100
having an alternative configuration within and around a handle. The
cryotherapeutic device 1100 includes a pre-cooling assembly 1102 and a
hub 1104 within a handle 1106. The pre-cooling assembly 1102 includes a
flexible tubular member 1108 extending from the hub 1104 and through a
bottom portion 1110 of the handle 1106. The hub 1104 can include an
elongated exhaust portal 1112 extending through the bottom portion 1110,
and a control-wire conduit 1114 can extend from the hub 1104 through the
bottom portion 1110. In one embodiment, the tubular member 1108 includes
a helical portion 1116 spaced apart from the exhaust portal 1112. The
handle 1106 also can be insulated to prevent heat loss to the atmosphere
and improve pre-cooling efficiency.

Cryotherapeutic-Device Components

[0180] Having in mind the foregoing discussion of cryotherapeutic devices
configured in accordance with several embodiments of the present
technology, a variety of different cooling assemblies, occlusion members,
and other cryotherapeutic-device components are described below with
reference to FIGS. 12-55. It will be appreciated that the
cryotherapeutic-device components described below and/or specific
features of the cryotherapeutic-device components described below can be
used with the cryotherapeutic system 100 shown in FIG. 1, used in a
standalone or self-contained handheld device, or used with another
suitable system. For ease of reference, throughout this disclosure
identical reference numbers are used to identify similar or analogous
components or features, but the use of the same reference number does not
imply that the parts should be construed to be identical. Indeed, in many
examples described herein, the identically-numbered parts are distinct in
structure and/or function.

[0181] Several embodiments of cryotherapeutic-device components described
below can be configured to facilitate one or more treatment objectives
related to cryogenic renal-nerve modulation. For example, several
embodiments of applicators described below are configured to apply
cryogenic cooling in a desirable localized or overall treatment pattern.
A desirable localized treatment pattern can include, for example,
partially-circumferential cooling at one or more longitudinal segments of
a renal artery or a renal ostium. A desirable overall treatment pattern
can include a combination of localized treatment patterns at a treatment
site. For example, a desirable overall treatment pattern can be a
partially-circumferential or a fully-circumferential treatment pattern in
a plane perpendicular to a renal artery or a renal ostium. To facilitate
a desirable localized or overall treatment pattern, an applicator
configured in accordance with several embodiments of the present
technology can have more than one heat-transfer portion, such as a
primary heat-transfer portion and a secondary heat-transfer portion. When
a cooling assembly including such an applicator is operating in a
deployed state, a primary heat-transfer portion of the applicator can
have a heat-transfer rate sufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation. A secondary heat-transfer portion of
the applicator can have a lower heat-transfer rate during operation, such
as a heat-transfer rate insufficient to cause therapeutically-effective,
cryogenic renal-nerve modulation. The positioning of the primary and
secondary heat-transfer portions can correspond to a desirable localized
or overall treatment pattern.

[0182] Several embodiments of applicators described below include features
configured to affect the positioning of primary and secondary
heat-transfer portions. Such features can include, for example, features
related to (a) differential convective heat-transfer within an
applicator, (b) differential conductive heat-transfer through an
applicator, and/or (c) differential contact or spacing between an
applicator and a renal artery or a renal ostium at a treatment site.
Features related to differential convective heat transfer can include,
for example, refrigerant supply tubes and orifices configured to
selectively direct expansion of refrigerant toward different portions of
an applicator. Features related to differential conductive heat transfer
through an applicator can include, for example, additional balloons
(e.g., non-cooling balloons and balloons having low levels of cooling),
differential composition (e.g., low thermal conductivity and high thermal
conductivity materials), differential thicknesses (e.g., balloon-wall
thicknesses), and thermally-insulative structures (e.g., elongated,
thermally-insulative members within balloons or attached to balloon
walls). Features related to differential contact or spacing between an
applicator and a renal artery or a renal ostium can include, for example,
additional balloons, and characteristics of complex balloons, such as
shape (e.g., helical, curved, longitudinally-asymmetrical, and
radially-asymmetrical), surface differentiation (e.g., recesses, groves,
protrusions, and projections), and differential expansion (e.g.,
partially-constrained expansion).

[0183] Several embodiments of applicators described below are also
configured to facilitate sizing, such as delivery at a reduced (e.g.,
low-profile) cross-sectional dimension and deployment at a
cross-sectional dimension suitable for providing
therapeutically-effective treatment to renal arteries and/or renal
ostiums having different sizes. For example, several embodiments of
applicators described below include a balloon that is at least partially
collapsed when an associated cooling assembly is in a delivery state and
at least partially expanded when an associated cooling assembly is in a
deployed state. Features related to sizing can include, for example,
balloon composition (e.g., compliant and non-compliant materials),
additional balloons, and characteristics of complex balloons, such as
shape (e.g., compliant and non-compliant shapes). Non-compliant materials
(e.g., polyethylene terephthalate) can have compliance (e.g.,
elasticity), for example, from about 0% to about 30%. Compliant materials
(e.g., polyurethane and other thermoplastic elastomers) can have
compliance, for example, from about 30% to about 500%. Non-compliant
materials typically have greater strength (e.g., higher pressure ratings)
than compliant materials. Several embodiments of applicators described
below can be configured to facilitate a desirable level of occlusion of a
renal artery and/or a renal ostium. For example, several embodiments of
applicators described below are configured to be partially occlusive,
such as to apply therapeutically-effective cooling for renal nerve
modulation at a treatment site without preventing blood flow through the
treatment site. Features related to partial occlusion include, for
example, characteristics of complex balloons, such as shape (e.g.,
helical, curved, longitudinally-asymmetrical, and radially-asymmetrical)
and differential expansion (e.g., partially-constrained expansion). Full
occlusion, such as complete or near-complete blockage of blood-flow
through a renal artery or a renal ostium can be desirable with regard to
certain treatments. Features related to full occlusion can include, for
example, any suitable feature related to sizing. As described below,
cryotherapeutic devices configured in accordance with several embodiments
of the present technology can include an occlusion member, such as an
expandable member of a cooling assembly (e.g., a balloon defining an
expansion chamber) or a separate occlusion member (e.g., proximal to a
cooling assembly). An occlusion member can be combined with any suitable
applicator described herein to provide occlusion in conjunction with
features associated with the applicator.

[0184] Cooling assemblies configured in accordance with the present
technology can include structures that take advantage of frozen and/or
liquid blood proximate an applicator to facilitate one or more treatment
objectives related to cryogenic renal-nerve modulation. Frozen and/or
liquid blood proximate an applicator can affect factors such as heat
transfer, sizing, and occlusion. For example, several embodiments can be
configured to freeze blood around an applicator to cause full or partial
occlusion. In some cases, therapeutically-effective cooling can occur
through a layer of frozen blood (e.g. a layer of frozen blood having a
thickness less than about 0.8 mm, 1 mm, or 1.2 mm). A balloon can be
configured such that frozen blood having a thickness through which
therapeutically-effective cooling can occur is formed between a primary
heat-transfer portion of the balloon and a renal artery or a renal
ostium. This layer, for example, can facilitate sizing or a desired level
of occlusion. Moreover, a balloon can be configured such that frozen
blood having a thickness through which therapeutically-effective cooling
cannot occur (e.g., a thickness greater than about 0.8 mm, 1 mm, or 1.2
mm) is formed between a secondary heat-transfer portion and a renal
artery or a renal ostium. Such balloons can include, for example,
recessed and non-recessed portions and other suitable structures as
described in greater detail below.

Convective Heat Transfer

[0185] FIGS. 12-16B illustrate several embodiments of cryotherapeutic
devices that can use differential convective heat-transfer to affect a
treatment. Features related to convective heat transfer within an
applicator can facilitate one or more treatment objectives of cryogenic
renal-nerve modulation, such as a desirable localized or overall
treatment pattern. Such features can include, for example, refrigerant
supply tubes and orifices configured to selectively direct expansion of
refrigerant toward different portions of an applicator.

[0186]FIG. 12 illustrates a portion of a cryotherapeutic device 1200
including a cooling assembly 1202 at a distal portion 1204 of an
elongated shaft 1206 defining an exhaust passage. As described above, the
distal portion 1204 can have a step 1208 and the cooling assembly 1202
can include an applicator 1210 having a plurality of heat transfer
portions (individually identified as 1211a-d). The applicator 1210 also
can have a balloon 1212 with a distal neck 1214, and the balloon 1212 can
define an expansion chamber configured to generate and deliver cryogenic
cooling. The device 1200 can further include an elongated guide member
1216a, a first supply tube 1218 defining a first supply lumen, and a
second supply tube 1220 defining a second supply lumen. The guide member
1216a can define a guide-wire lumen shaped to receive a guide wire 1216b,
as described in greater detail above. Guide members described with
respect to other cryotherapeutic-device components described herein can
be similarly configured, although for clarity of illustration, associated
guide wires typically are not shown. In the illustrated embodiment, the
guide member 1216a has a straight end and extends to the distal neck
1214. Alternatively, the guide member 1216a can include a rounded end
and/or an end that extends beyond the distal neck 1214. Similarly, in
other cryotherapeutic-device components described herein, illustrated
ends of guide members and/or supply tubes that exit distal portions of
balloons can have various suitable shapes (e.g., atraumatic shapes) and
can extend varying distances relative to distal necks of balloons.

[0187] The first supply tube 1218 can include a first angled distal
portion 1222, and the cooling assembly 1202 can include a first orifice
1224 at the end of the first angled distal portion 1222. Similarly, the
second supply tube 1220 can include a second angled distal portion 1226,
and the cooling assembly can include a second orifice 1228 at the end of
the second angled distal portion. The first and second angled distal
portions 1222, 1226 of the illustrated embodiment are longitudinally and
radially spaced apart along and about the length of the cooling assembly
1202. In several other embodiments, the first and second angled distal
portions 1222, 1226 have the same longitudinal and/or radial position, or
another configuration. When the cooling assembly 1202 is in a deployed
state, refrigerant can flow through the first and second supply tubes
1218, 1220, flow through the first and second angled distal portions
1222, 1226, respectively, and flow out the first and second orifices
1224, 1228, respectively. The first and second angled distal portions
1222, 1226 can direct expanded refrigerant toward the heat-transfer
portions 1211a and 1211d, respectively. As a result, when refrigerant
flows out of the first and second orifices 1224, 1228, the heat-transfer
portions 1211a and 1211d can have higher overall and particularly
convective heat-transfer rates relative to other heat-transfer portions
of the applicator 1210. This variation in heat-transfer rate can
correspond to a desired cooling pattern, such as a
partially-circumferential cooling pattern at some or all longitudinal
segments of the applicator 1210. The difference in heat-transfer rate can
vary depending on a distance from the heat-transfer portions 1211a and
1211d. A functionally significant difference in heat-transfer rate can
separate the heat-transfer portion 1211a from the heat-transfer portion
1211c, which is generally circumferentially opposite to the heat-transfer
portion 1211a. Similarly, a functionally significant difference in
heat-transfer rate can separate the heat-transfer portion 1211d from the
heat-transfer portion 1211b, which is generally circumferentially
opposite to the heat-transfer portion 1211d. In several embodiments, the
heat-transfer portions 1211a and 1211d have heat-transfer rates
sufficient to cause therapeutically-effective renal nerve modulation,
while the heat-transfer portions 1211b and 1211c have heat-transfer rates
insufficient to cause therapeutically-effective renal nerve modulation.

[0188] The first and second supply tubes 1218, 1220 can be configured, for
example, to direct expansion of refrigerant at angles about 45°
offset from the length of the applicator 1210 or the length of the
cooling assembly 1202. In several other embodiments, one or more supply
tubes are configured to direct refrigerant at an angle from about
15° to about 90° relative to a length of an applicator or a
cooling assembly, such as from about 30° to about 45°, or
from about 30° to about 40°. Additionally, the first supply
tube 1218 can be at a different angle than the second supply tube 1220.
The longitudinal distance between a first orifice 1224 and a second
orifice 1228 of a cooling assembly configured in accordance with several
embodiments of the present technology can be, for example, from about 1
mm to about 20 mm, such as from about 2 mm to about 15 mm, or from about
3 mm to about 10 mm.

[0189] Cooling assemblies configured in accordance with several
embodiments of the present technology can alternatively include a supply
tube or lumen having a curved and/or helical portion. FIG. 13 illustrates
a portion of a cryotherapeutic device 1300 including a cooling assembly
1302 at a distal portion 1304 of an elongated shaft 1306 defining an
exhaust passage open at the end of the distal portion 1304. The distal
portion 1304 can have a step 1307 and the cooling assembly 1302 can
include an applicator 1308 having a first heat-transfer portion 1309 and
a second heat-transfer portion 1310. The first and second heat-transfer
portions 1309, 1310 are elongated and radially spaced apart around the
length of the cooling assembly 1302. The applicator 1308 also can have a
balloon 1311 that can define an expansion chamber configured to generate
and deliver cryogenic cooling. The device 1300 can further include an
elongated guide member 1312 and a supply tube 1313 extending along the
length of the shaft 1306. Within the balloon 1311, the supply tube 1313
can include a helical portion 1314 that exits the distal portion 1304 and
wraps around the distal portion 1304 (e.g., the distal portion 1304 can
define a central axis of the helical portion 1314). The cooling assembly
1302 can include a plurality of orifices (individually identified as
1316a-e) laterally spaced apart along the helical portion 1314. In the
illustrated embodiment, if the helical portion 1314 were straightened,
the orifices 1316a-e would be generally radially aligned. In this
embodiment, the shape of the helical portion 1314 causes the orifices
1316a-e to point in different radial directions. In other embodiments,
the helical portion 1314 can have a different number and/or orientation
of orifices 1316a-e.

[0190] The helical portion 1314 locates the orifices 1316a-e closer to the
balloon 1311 than they would be if the supply tube 1312 were straight.
This can cause refrigerant exiting the orifices 1316a-e to contact the
balloon 1311 at higher velocities and increase the amount of convective
cooling at corresponding heat-transfer portions of the balloon 1311. This
can also provide more control of the size and spacing of where
refrigerant first contacts the balloon 1311. Cooling assemblies
configured in accordance with several embodiments of the present
technology can include orifices spaced apart greater than about 0.01 mm
(e.g., greater than about 0.1 mm, greater than about 0.5 mm, or greater
than about 1 mm) from central longitudinal axes of cooling assemblies
when the cooling assemblies are in a deployed state. For example,
orifices in several embodiments can be between about 0.01 mm and about 4
mm or between about 0.1 mm and about 2 mm from central longitudinal axes
of cooling assemblies when the cooling assemblies are in a deployed
state. Similarly, cooling assemblies configured in accordance with
several embodiments of the present technology can include orifices spaced
apart by less than about 4 mm (e.g., less than about 2 mm, less than
about 1 mm, or less than about 0.5 mm) from balloons when the cooling
assemblies are in a deployed state. For example, orifices in several
embodiments can be between about 0.1 mm and about 4 mm or between about
0.5 mm and about 2 mm apart from balloons when the cooling assemblies are
in a deployed state. Furthermore, cooling assemblies configured in
accordance with several embodiments of the present technology can include
an orifice positioned such that a distance from a central longitudinal
axis of a cooling assembly to the orifice is not less than about 20%
(e.g., not less than about 25%, 40%, or 60%) of a distance from the
central longitudinal axis to an inner surface of a balloon in a plane at
the orifice and perpendicular to the central longitudinal axis.

[0191] In the illustrated embodiment, the orifices 1316a, 1316c, 1316e
point generally toward an upper half of the balloon 1311, while the
orifices 1316b, 1316d point generally toward a lower half of the balloon
1311. When the cooling assembly 1302 is in a deployed state, refrigerant
flow through orifices 1316a, 1316c, 1316e produces the first
heat-transfer portion 1309, while refrigerant flow through orifices
1316b, 1316d produces the second heat-transfer portion 1310. As a result
of the refrigerant flow, the first and second heat-transfer portions
1309, 1310 can have higher overall and particularly convective
heat-transfer rates relative to other heat-transfer portions of the
applicator 1308. This variation in heat-transfer rate can correspond to a
desired cooling pattern, such as a partially-circumferential cooling
pattern at some or all longitudinal segments of the applicator 1308. In
several embodiments, the first and second heat-transfer portions 1309,
1310 have heat-transfer rates sufficient to cause
therapeutically-effective renal nerve modulation, while portions of the
applicator 1308 between the first and second heat-transfer portions 1309,
1310 have heat-transfer rates insufficient to cause
therapeutically-effective renal nerve modulation.

[0192]FIG. 14 illustrates a portion of a cryotherapeutic device 1400 that
differs from the device 1300 of FIG. 13 primarily with respect to an
exhaust configuration. The device 1400 includes a cooling assembly 1402
at a distal portion 1404 of an elongated shaft 1406 defining an exhaust
passage. The distal portion 1404 can have a step 1407, a plurality of
exhaust openings 1408, and a rounded end 1409. The cooling assembly 1402
can include an applicator 1410 with a balloon 1411 having a distal neck
1412 and the balloon 1411 can define an expansion chamber configured to
generate and deliver cryogenic cooling. The device 1400 can further
include a supply tube 1413 extending along the length of the shaft 1406
and into the balloon 1411. Within the balloon 1411, the supply tube 1413
can include a helical portion 1414 that exits the distal portion 1404 and
wraps around the distal portion 1404 (e.g., the distal portion 1404 can
define a central axis of the helical portion 1414). The helical coils of
the helical portion 1414 can be located between the exhaust openings
1408. The cooling assembly 1402 can include a plurality of orifices
(individually identified as 1416a-d) laterally spaced apart along the
helical portion 1414. In the illustrated embodiment, the distal portion
1404 is sufficiently narrow to allow the helical portion 1414 to wrap
around the distal portion 1404 generally without extending beyond the
diameter of the shaft 1406 proximal to the distal portion 1404.
Accordingly, the cooling assembly 1402 in a delivery state can be
configured to fit within a delivery sheath sized according to the shaft
1406. The plurality of exhaust openings 1408 can promote exhaust flow and
mitigate any flow restriction associated with the sizing of the distal
portion 1404. Thus, as discussed above, the relatively high density of
expanded refrigerant entering the exhaust passage can allow the distal
portion 1404 to be sized down without necessarily causing an unsuitable
increase in back pressure.

[0193] Similar to the orifices 1316a-e of the device 1300 of FIG. 13, the
orifices 1416a-d in the illustrated embodiment are laterally spaced apart
along the helical portion 1414. However, unlike the orifices 1316a-d of
the device 1300 of FIG. 13, the orifices 1416a-d in the illustrated
embodiment are configured to direct refrigerant flow in different radial
directions around the length of the cooling assembly 1402. Specifically,
the orifices 1416a-d are configured to direct refrigerant flow in
directions radially spaced apart by increments of about 90°. The
orifices 1416a-d are sized to cause corresponding heat-transfer portions
having circumferential arcs greater than about 90°. As a result,
the projected circumference of the heat-transfer portions corresponding
to the orifices 1416a-d is generally fully circumferential, while being
partially circumferential in particular longitudinal segments of the
cooling assembly 1402.

[0194] As discussed above with reference to FIG. 13, locating primary
refrigerant expansion areas closer to a balloon can facilitate convective
heat transfer. FIGS. 15A-15B illustrate a portion of a cryotherapeutic
device 1500 that also can be configured to locate primary refrigerant
expansion areas closer to a balloon. The device 1500 includes a cooling
assembly 1502 at a distal portion 1504 of an elongated shaft 1506
defining an exhaust passage. The distal portion 1504 can have a step
1507, and the cooling assembly 1502 can include an applicator 1508 with
an outer balloon 1510 that can define an expansion chamber configured to
generate and deliver cryogenic cooling. The device 1500 can further
include a supply tube 1512 and an inner balloon 1514. The supply tube
1512 has a rounded end 1516 and can extend along the length of the shaft
1506 and through a distal portion of the outer balloon 1510. The inner
balloon 1514 extends around a portion of the supply tube 1512 within the
outer balloon 1510. In several other embodiments configured in accordance
with the present technology, a supply tube 1512 terminates within an
inner distributor, such as the inner balloon 1514, and/or the device can
include a guide member that can extend through the inner balloon 1514 and
through the distal portion of the outer balloon 1510. With reference
again to the embodiment of the device 1500 shown in FIGS. 15A-15B, the
portion of the supply tube 1512 within the inner balloon 1514 can include
supply-tube orifices 1518. The cooling assembly 1502 can include
inner-balloon orifices 1520 distributed in a helical arrangement or other
suitable arrangement on the inner balloon 1514. The inner-balloon
orifices 1520 can be, for example, laser-cut holes in the inner balloon
1514. When the cooling assembly 1502 is in a delivery state, the outer
balloon 1510 and the inner balloon 1514 can be at least partially
collapsed to fit within a delivery sheath.

[0195] When the cooling assembly 1502 is in a deployed state, refrigerant
can flow from the supply tube 1512, through the supply-tube orifices
1518, and into the inner balloon 1514. The supply-tube orifices 1518 can
be large enough to allow refrigerant to enter the inner balloon 1514
without liquid-to-gas phase change of a significant portion of liquid
refrigerant (e.g., a majority of liquid refrigerant). For example, in the
deployed state, a refrigerant absolute vapor pressure within the inner
balloon 1514 outside the supply tube 1512 can be from about 40% to about
100% of a refrigerant absolute vapor pressure within the portion of the
supply tube within the inner balloon 1514, such as from about 20% to
about 100%, or from about 33% to about 100%. A first free-passage area
equal to the total free-passage area of the inner-balloon orifices 1520
can be less than a second free-passage area equal to the total
free-passage area of the supply-tube orifices 1518. The size and/or
number of inner-balloon orifices 1520 can be selected to control the
first free-passage area. Similarly, the size and/or number of supply-tube
orifices 1518 can be selected to control the second free-passage area.
From the inner balloon 1514, refrigerant can expand through the
inner-balloon orifices 1520 to cool one or more corresponding
heat-transfer portions of the applicator 1508. In particular, the
inner-balloon orifices 1520 can be configured to cool a generally helical
heat-transfer portion.

[0196] FIGS. 16A-16B illustrate a cryotherapeutic device 1600 that differs
from the cooling assembly 1500 of FIG. 15A with respect to an
outer-balloon shape. The device 1600 includes a cooling assembly 1602
including an applicator 1604 with an outer balloon 1606 having a raised
helical portion 1608 and a recessed portion 1610. The inner surface of
the raised helical portion 1608 can be configured to receive expanded
refrigerant from the inner-balloon orifices 1520, and the shape of the
inner surface of the raised helical portion 1608 can help to localize
increased convective cooling at the raised helical portion 1608. The
recessed portion 1610 is generally configured not to contact a renal
artery or a renal ostium. Localizing increased convective cooling to the
raised helical portion 1606 can promote cooling efficiency as well as
cooling-location selectivity. The raised helical portion 1608 can
correspond to a heat-transfer portion having a higher heat-transfer rate
than other heat-transfer portions of the applicator 1604, such as a
heat-transfer portion corresponding to the recessed portion 1610. For
example, during operation, the raised helical portion 1608 can correspond
to a heat-transfer portion having a heat-transfer rate sufficient to
cause therapeutically-effective renal nerve modulation, while another
heat-transfer portion of the applicator (e.g., a heat-transfer portion
corresponding to the recessed portion 1610) has a heat-transfer rate
insufficient to cause therapeutically-effective renal nerve modulation.

Conductive Heat Transfer

[0197] FIGS. 17A-22B illustrate several embodiments of cryotherapeutic
devices that can use differential conductive heat-transfer to affect a
treatment. Features related to conductive heat transfer through an
applicator can facilitate one or more treatment objectives of cryogenic
renal-nerve modulation, such as a desirable localized or overall
treatment pattern. In several embodiments, the devices control conduction
using thermally-insulative members. Features related to differential
conductive heat transfer through an applicator can include, for example,
additional balloons (e.g., non-cooling balloons and balloons having low
levels of cooling), differential composition (e.g., low thermal
conductivity and high thermal conductivity materials), differential
thicknesses (e.g., balloon-wall thicknesses), and thermally-insulative
structures (e.g., elongated, thermally-insulative members within balloons
or attached to balloon walls).

[0198] FIGS. 17A-17B illustrate a portion of a cryotherapeutic device 1700
including a cooling assembly 1702 at a distal portion 1704 of an
elongated shaft 1706 defining an exhaust passage. The distal portion 1704
can have a step 1707, and the cooling assembly 1702 can include an
applicator 1708 having a balloon 1710 configured to contact a renal
artery or a renal ostium. The applicator 1708 can further include a
plurality of elongated, thermally-insulative members 1711 with lengths
generally parallel to the length of the cooling assembly 1702 and
radially spaced apart around the circumference of the cooling assembly
1702. The balloon 1710 can define an expansion chamber configured to
generate and deliver cryogenic cooling. The device 1700 can further
include a supply tube 1712 extending along the length of the shaft 1706
and into the balloon 1710, and the cooling assembly 1702 can include an
orifice 1714 at the end of the supply tube 1712. During operation when
the cooling assembly 1702 is in a deployed state, the
thermally-insulative members 1711 can reduce conductive cooling through
adjacent portions of the balloon 1710. For example, portions of the
balloon 1710 between the thermally-insulative members 1711 can have
heat-transfer rates sufficient to cause therapeutically-effective renal
nerve modulation, while portions of the balloon at the
thermally-insulative members 1711 can have lower heat-transfer rates,
such as heat-transfer rates insufficient to cause
therapeutically-effective renal nerve modulation. The
thermally-insulative members 1711 can be elongated and generally
continuous along the length of portions of the applicator 1708.
Accordingly, heat-transfer portions corresponding to portions of the
balloon 1710 between the thermally-insulative members 1711 can be
generally non-circumferential at longitudinal segments of the cooling
assembly 1702.

[0199] The thermally-insulative members 1711 can include a primary
material having a thermal conductivity lower than or equal to a thermal
conductivity of a primary material of the balloon 1710. In several
embodiments, the thermally-insulative members 1711 have different
compositions than the balloon 1710 and are attached to an inner surface
of the balloon 1710. Several other embodiments can include
thermally-insulative members 1711 that are compositionally similar to
(e.g., the same as) or different than the balloon 1710. Suitable primary
materials for a thermally-insulative member configured in accordance with
several embodiments of the present technology include
thermally-insulative polymer foams (e.g., polyurethane foams). In several
embodiments, a thermally-insulative member 1711 can be integrally formed
with a balloon 1710 or attached to a balloon 1710.

[0200] FIGS. 18A-18B illustrate a portion of a cryotherapeutic device 1800
similar to the device 1700 of FIGS. 17A-17B except with regard to a
configuration of thermally-insulative members. Thermally-insulative
members configured in accordance with several embodiments of the present
technology can have different insulative properties in the delivery state
than in deployed state. For example, a thermally-insulative member can be
configured to be filled with a filler material in the deployed state. The
device 1800 includes a cooling assembly 1802 having an applicator 1804
with a balloon 1806 that can define an expansion chamber configured to
generate and deliver cryogenic cooling. The applicator 1804 also includes
a plurality of thermally-insulative members 1808. The device 1800 can
further include a filler tube 1810, and the thermally-insulative members
1808 can be configured to be filled in the deployed state via the filler
tube 1810. In the illustrate embodiment, the filler tube 1810 includes a
main portion 1812 and four branches 1814, in which the branches fluidly
connect the main portion with one of the thermally-insulative members
1808. The thermally-insulative members 1808 and the filler tube 1810 are
fluidly separate from the expansion chamber within the balloon 1806.

[0201] The filler tube 1810 has a proximal portion (not shown) configured
to receive filler material from a filler-material source (not shown) from
outside the vasculature. The filler tube 1810 and the
thermally-insulative members 1808 can be configured to be fully, mostly,
or partially collapsed in the delivery state. This can be useful to allow
the introduction of fluidic filler material in the delivery state without
the need to vent displaced gas. Several other embodiments can include a
filler tube that is generally not collapsible and a thermally-insulative
member configured to receive displaced gas or liquid from such a filler
tube. A proximal portion of a filler tube configured in accordance with
several embodiments of the present technology can be fluidly connected to
a filler port, such as a filler port including syringe adapter, such as a
syringe adapter including a diaphragm configured to be punctured with a
needle of a syringe containing filler material. Such a filler port can be
configured, for example, to reduce (e.g., prevent) passage of air before,
during, and/or after passage of filler material. However, in several
embodiments, air can be a suitable filler material. Other components of
cryotherapeutic devices configured in accordance with several embodiments
of the present technology including a filler tube (including such
embodiments described herein) can be similarly configured. Suitable
filler materials for use with cryotherapeutic devices configured in
accordance with several embodiments of the present technology include
liquids (e.g., saline), gases (e.g., air), biologically inert materials,
and radiopaque materials (e.g., contrast agents).

[0202] Although four thermally-insulative members are shown in FIGS.
17A-18B, cooling assemblies configured in accordance with several
embodiments of the present technology can include any suitable number of
thermally-insulative members, such as at least one or more
thermally-insulative members. Additionally, thermally-insulative members
configured in accordance with several embodiments of the present
technology can be generally separate elements or portions of a single
element and can have a variety of suitable shapes.

[0203] FIGS. 19A-19C illustrate a portion of a cryotherapeutic device
1900. Referring to FIG. 19A, the device 1900 can include a cooling
assembly 1902 at a distal portion 1904 of an elongated shaft 1906
defining an exhaust passage. The distal portion 1904 can have a step
1907, and the cooling assembly 1902 can include an applicator 1908 with a
balloon 1910 that can define an expansion chamber configured to generate
and deliver cryogenic cooling. The device 1900 can further include a
supply tube 1912 extending along the length of the shaft 1906 and into
the balloon 1910, and the cooling assembly 1902 can include an orifice
1914 at an end of the supply tube 1912. The device 1900 can further
include a helical thermally-insulative member 1916 that can be, for
example, a thicker portion of the balloon 1910 with the extra thickness
at an inner surface of the balloon 1910 (i.e., an outer surface of the
balloon 1910 can be generally smooth or otherwise even at the helical
thermally-insulative member 1916 and around the helical
thermally-insulative member 1916). During operation when the cooling
assembly 1902 is in a deployed state, the helical thermally-insulative
member 1916 can correspond to a heat-transfer portion of the applicator
1908 having a lower heat-transfer rate than other portions of the
applicator 1908. For example, a heat-transfer rate of a portion of the
applicator 1908 apart from the helical thermally-insulative member 1916
can be sufficient to cause therapeutically-effective renal nerve
modulation during operation, while a heat-transfer rate of a portion of
the applicator 1908 at the helical thermally-insulative member 1916 can
be insufficient to cause therapeutically-effective renal nerve
modulation. FIGS. 19B and 19C are cross-sectional views of the applicator
1908 at different longitudinal positions. As shown in FIGS. 19B and 19C,
the circumferential position of the helical thermally-insulative member
1916 changes along the length of the cooling assembly 1902 such that the
portion of the balloon 1910 apart from the helical thermally-insulative
member 1916 is generally non-circumferential in longitudinal segments
along the length of the cooling assembly 1902.

[0204] FIGS. 20A-20C illustrate a portion of a cryotherapeutic device 2000
similar to the device 1900 of FIGS. 19A-19C except with regard to a
thermally-insulative member shape. Referring to FIG. 20A, the device 2000
includes a cooling assembly 2002 having an applicator 2004 with a balloon
2006 that can define an expansion chamber configured to generate and
deliver cryogenic cooling. The applicator 2004 also includes a
thermally-insulative member 2008 generally resembling an intertwined
double helix (e.g., an intertwined right-handed helix and left-handed
helix). A heat-transfer portion of the applicator 2004 at the
thermally-insulative member 2008 generally isolates heat-transfer
portions of the applicator 2004 apart from the thermally-insulative
member 2008. The thermally-insulative member 2008 can be configured to
collapse and/or expand with the balloon 2006 when the cooling assembly
2002 moves between the delivery state and the deployed state. For
example, if the balloon 2006 is generally flexible and non-compliant, the
thermally-insulative member 2008 can be either generally flexible and
compliant or non-compliant. If the balloon 2006 is generally compliant,
the thermally-insulative member 2008 can be generally compliant so as to
compliantly expand and contract in conjunction with the balloon 2006. The
thermally insulative members 1716, 1808 shown in FIGS. 17A-18B, and the
helical thermally-insulative member 1916 shown in FIGS. 19A-19B, can be
similarly configured relative to the corresponding balloons 1710, 1806,
1910. In several embodiments of the present technology, a
thermally-insulative member has a modulus of elasticity between about 50%
and about 150% of a modulus of elasticity of a corresponding balloon,
such as between about 20% and about 140%, or between about 33% and about
130%.

[0205] Thermally-insulative members configured in accordance with
additional embodiments of the present technology can be fully or
partially attached to a corresponding balloon, or in other embodiments,
the thermally-insulative members are not attached to the balloon. When a
thermally-insulative member is only partially attached or not attached to
a corresponding balloon, expansion and/or contraction of the
corresponding balloon can be relatively independent of the
thermally-insulative member. FIGS. 21A-21C illustrate a portion of a
cryotherapeutic device 2100 including a cooling assembly 2102 at a distal
portion 2104 of an elongated shaft 2106 defining an exhaust passage. The
distal portion 2104 can have a step 2107 and a rounded lip 2108. The
cooling assembly 2102 can include an applicator 2109 with a balloon 2110
having a distal neck 2111 and the balloon 2110 can define an expansion
chamber configured to generate and deliver cryogenic cooling. The device
2100 can further include an elongated guide member 2112 and a supply tube
2114 extending along a length of the shaft 2106 and into the balloon
2110. The cooling assembly 2102 can include an orifice 2116 at the end of
the supply tube. In the illustrated embodiment, the guide member 2112
extends through to the distal neck 2111. The applicator 2109 further
includes a first elongated, thermally-insulative member 2118 and a second
elongated, thermally-insulative member 2120. The first and second
elongated, thermally-insulative members 2118, 2120 are not attached to
the balloon 2110. Instead, the first and second elongated,
thermally-insulative members 2118, 2120 are attached to an inner surface
of the distal portion 2104.

[0206] When the cooling assembly 2102 is in a deployed state, the first
and second thermally-insulative members 2118, 2120 can be movable
relative to the balloon 2110 in response to gravity. The first and second
thermally-insulative members 2118, 2120 can move over the rounded lip
2108 as they settle within the balloon. As shown in FIG. 21A, the first
and second thermally-insulative members 2118, 2120 can settle along a
lower portion of the balloon 2110. As shown in FIG. 21B, the first and
second thermally-insulative members 2118, 2120 have cross-sectional areas
resembling rounded triangles. In other embodiments, a similar
thermally-insulative member can have a different cross-sectional area. A
rounded triangular cross-sectional area can be particularly useful to
increase a contact area between a side of a generally unattached
thermally-insulative member and an inner surface of a balloon while
preventing multiple generally unattached thermally-insulative members
from overlapping. With reference to FIG. 21c, the device 2100 is shown in
the delivery state within a delivery sheath 2122. As shown in FIG. 21c,
the first and second thermally-insulative members 2118, 2120 can collapse
with the balloon 2110 in the delivery state.

[0207] FIGS. 22A-22B illustrate a portion of a cryotherapeutic device 2200
similar to the device 2100 of FIGS. 21A-21C except with regard to a
configuration of thermally-insulative members. The device 2200 includes a
cooling assembly 2202 having an applicator 2204 with a balloon 2206 that
can define an expansion chamber configured to generate and deliver
cryogenic cooling. The applicator 2204 also includes a first elongated,
thermally-insulative member 2208 and a second thermally-insulative member
2210. The device 2200 can further include a filler tube 2212 and the
first and second thermally-insulative members 2208, 2210 can be
configured to be filled in the deployed state via the filler tube 2212.
The filler tube 2212 can include a hub 2214 where it branches into the
first and second thermally-insulative members 2208, 2210. As discussed
above with reference to the thermally-insulative members 1808 of the
device 1800 shown in FIGS. 18A-18B, the first and second
thermally-insulative members 2208, 2210 and the filler tube 2212 can be
fluidly separate from the balloon 2206. The filler tube 2212 can have a
proximal portion (not shown) configured to receive filler material from
outside the vasculature. The filler tube 2212 and the first and second
thermally-insulative members 2208, 2210 can be configured to be fully,
mostly, or partially collapsed when the cooling assembly 2202 is in a
delivery state.

[0208] A cooling assembly configured in accordance with several
embodiments of the present technology can include one or more
thermally-insulative members having a variety of suitable shapes to cause
different patterns of heat-transfer portions around an applicator. A
pattern can be selected, for example, so that a generally uninterrupted
heat-transfer portion at a thermally-insulative member can be large
enough to sufficiently localize cooling therapeutically-effective for
renal nerve modulation (e.g., such that cooling therapeutically-effective
for renal nerve modulation generally does not bridge across a
heat-transfer portion at a thermally-insulative member). In addition or
instead, a pattern can be selected, for example, so that a heat-transfer
portion spaced apart from a thermally-insulative member is large enough
to allow therapeutically-effective cooling for renal nerve modulation.
Heat transfer is proportional to area, so if a heat-transfer portion
spaced apart from a thermally-insulative member is too small, the total
heat transfer through that part of the heat transfer portion can be
inadequate to cause therapeutically-effective cooling for renal nerve
modulation.

Complex Balloons

[0209] FIGS. 23A-37 illustrate several embodiments of cryotherapeutic
devices that include complex balloons which can facilitate one or more
treatment objectives related to cryogenic renal-nerve modulation, such as
a desirable localized or overall treatment pattern, sizing, and partial
occlusion. Complex balloons can have a variety of suitable
characteristics, such as shape (e.g., helical, curved,
longitudinally-asymmetrical, and radially-asymmetrical), surface
differentiation (e.g., recesses, groves, protrusions, and projections),
and differential expansion (e.g., partially-constrained expansion).

[0210] FIGS. 23A-23B illustrate a portion of a cryotherapeutic device 2300
including a cooling assembly 2302 at a distal portion 2304 of an
elongated shaft 2306 defining an exhaust passage. The distal portion 2304
can have a step 2307, a first exhaust port 2308, a second exhaust port
2309, and a rounded end 2310. The cooling assembly 2302 can include an
applicator 2311 having a first balloon 2312 that defines a first
expansion chamber and a second balloon 2313 that defines a second
expansion chamber. The first balloon 2312 and the second balloon 2313 are
fluidly connected to the exhaust passage through the first exhaust port
2308 and the second exhaust port 2309, respectively. The device 2300 can
further include a supply tube 2314 extending along a length of the shaft
2306, and the cooling assembly 2302 can further include a first orifice
2316 and a second orifice 2318. The first orifice 2316 is aligned with
the first exhaust port 2308 such that refrigerant expands through the
first exhaust port 2308 and into the first balloon 2312, and the second
orifice 2318 is aligned with the second exhaust port 2309 such that
refrigerant expands through the second exhaust port 2309 and into the
second balloon 2313.

[0211] The first and second balloons 2312, 2313 are spaced apart along the
length of the cooling assembly 2302 and configured to expand laterally
across different partially-circumferential arcs along the length of the
cooling assembly 2302. When the cooling assembly 2302 is in a deployed
state, the first balloon 2312 can be configured to contact a first
partially-circumferential portion of an inner surface of a renal artery
or a renal ostium, and the second balloon 2313 can be configured to
contact a second partially-circumferential portion of the inner surface
of the renal artery or the renal ostium. The first and second
partially-circumferential portions can have a fully-circumferential
combined projection in a plane perpendicular to a length of the renal
artery or the renal ostium. Accordingly, when a treatment calls for
partially-circumferential cooling at longitudinal segments and a
fully-circumferential overall cooling pattern, the cooling assembly 2302
can be configured to facilitate such a treatment without repositioning
the cooling assembly 2302 during the treatment.

[0212] When the first and second balloons 2312, 2313 are both in the
deployed state, they can urge each other toward generally opposite sides
of an inner surface of a renal artery or a renal ostium. For example, the
distal portion 2304 can transfer forces between the first and second
balloons 2312, 2313 while a portion of the shaft 2306 proximal to the
distal portion holds the distal portion generally parallel to a length of
a renal artery or a renal ostium. During this and other operation, the
cooling assembly 2302 can be configured to be non-occlusive (i.e., to
less than fully occlude a renal artery or a renal ostium). For example,
the cooling assembly 2302 can be configured to allow a percentage of
normal blood flow through a renal artery or a renal ostium (e.g., at
least about 1%, at least about 10%, or at least about 25% of normal blood
flow).

[0213] FIGS. 24A-24B illustrate a portion of a cryotherapeutic device 2400
that differs from the device 2300 of FIGS. 23A-23B primarily with respect
to an exhaust configuration. The device 2400 includes a cooling assembly
2402 at a distal portion 2404 of an elongated shaft 2406 defining an
exhaust passage. The distal portion 2404 can have a step 2407, a first
exhaust port 2408, a second exhaust port 2409, and a rounded end 2410.
The cooling assembly 2402 can include an applicator 2411 having a first
balloon 2412 that defines a first expansion chamber and a second balloon
2413 that defines a second expansion chamber. The first balloon 2412 and
the second balloon 2413 are fluidly connected to the exhaust passage
through the first exhaust port 2408 and the second exhaust port 2409,
respectively. The device 2400 can further include a supply tube 2414
extending along a length of the shaft 2406 and having a first lateral
branch 2416 and a second lateral branch 2418. The cooling assembly 2402
can further include a first orifice 2420 at the end of the first lateral
branch 2416 open to the first balloon 2412 and a second orifice 2422 at
the end of the second lateral branch 2418 open to the second balloon
2413. Unlike the device 2300 shown in FIGS. 23A-23B, the device 2400
includes refrigerant supply and refrigerant exhaust at circumferentially
opposite sides of the distal portion 2404 for the first and second
balloons 2412, 2413. The first and second balloons 2412, 2413 extend
around fully-circumferential longitudinal segments of the distal portion
2404, but are attached to the distal portion 2404 and shaped so as to
expand asymmetrically about the distal portion 2404.

[0214] Cooling assemblies configured in accordance with several
embodiments of the present technology can include a different number of
partially-circumferential balloons from the cooling assemblies 2302, 2402
shown in FIGS. 23A-24B. For example, in several embodiments, the cooling
assembly 2302 can include the first balloon 2312 or the second balloon
2313 rather than both. Similarly, the cooling assembly 2402 can include
the first balloon 2412 or the second balloon 2413 rather than both. The
cooling assemblies 2302, 2402 shown in FIGS. 23A-24B also can include a
greater number of balloons, such as three or four balloons longitudinally
and radially spaced apart. Furthermore, the sizes of the balloons can
vary. For example, in several embodiments, the first and second balloons
2312, 2313 of the cooling assembly 2302 or the first and second balloons
2412, 2413 of the cooling assembly 2402 are configured to provide a
partially-circumferential overall cooling pattern.

[0215] Cooling assemblies configured in accordance with several
embodiments of the present technology can include applicators with
balloons having a variety of suitable surface characteristics, such as
surface characteristics configured to facilitate
partially-circumferential cooling at longitudinal segments alone or in
combination with a fully-circumferential overall cooling pattern. FIG. 25
illustrates a portion of a cryotherapeutic device 2500 including a
cooling assembly 2502 at a distal portion 2504 of an elongated shaft 2506
defining an exhaust passage. The distal portion 2504 can have a step
2507, and the cooling assembly 2502 can include an applicator 2508 with a
balloon 2510 that defines an expansion chamber and has a distal neck
2511, a helical recess 2512, and a non-recessed portion 2513. The device
2500 can further include an elongated guide member 2514 that extends
through the distal neck 2511, as well as a supply tube 2516 that extends
along the length of the shaft 2506 and into the balloon 2510. The cooling
assembly 2502 can further include an orifice 2518 at the distal end of
the supply tube 2516. When the cooling assembly 2502 is in a delivery
state, the helical recess 2512 can correspond to a heat-transfer portion
of the applicator 2508 having a lower heat-transfer rate than portions of
the applicator 2508 spaced apart from the helical recess 2512.

[0216] The space between the helical recess 2512 and an inner surface of a
renal artery or a renal ostium at a treatment site can thermally insulate
portions of the renal artery or the renal ostium closest to the helical
recess 2512 from a cryogenic temperature within the balloon 2510. For
example, frozen or liquid blood within this space can provide thermal
insulation. The depth of the helical recess 2512 relative to the
non-recessed portion 2513 can be, for example, a depth corresponding to a
thickness of material (e.g., liquid or frozen blood) sufficient to
thermally insulate a portion of a renal artery or a renal ostium from
cryogenic cooling within the balloon 2510. For example, the depth can be
between about 0.2 mm and about 2 mm, such as between about 0.3 mm and
about 1.5 mm. Recessed portions of balloons in several other embodiments
of cryotherapeutic-device components described herein can have similar
depths relative to non-recessed portions of the balloons.

[0217]FIG. 26 illustrates a portion of another embodiment of a
cryotherapeutic device 2600 including a cooling assembly 2602 at a distal
portion 2604 of an elongated shaft 2606 defining an exhaust passage. The
distal portion 2604 can have a step 2607, and the cooling assembly 2602
can include an applicator 2608 with a balloon 2610 that defines an
expansion chamber and has a distal neck 2611, a plurality of recesses
2612, and a non-recessed portion 2613. The recesses 2612 can be arranged
in a helical pattern around the circumference of the balloon 2610. The
cooling assembly 2602 can further include an elongated guide member 2614
that extends through the distal neck 2611. The device 2600 can also
include a supply tube 2616 that extends along the length of the shaft
2606 and into the balloon 2610. The cooling assembly 2602 can further
include an orifice 2618 at the distal end of the supply tube 2616. When
the cooling assembly 2602 is in a deployed state, the recesses 2612 and
the non-recessed portion 2613 can function similarly to the helical
recess 2512 and the non-recessed portion 2513 of the device 2500 shown in
FIG. 25.

[0218] FIGS. 27A-27C illustrate a portion of a cryotherapeutic device 2700
similar to the device 2600 of FIG. 26, but the device 2700 is configured
to be less occlusive within a renal artery or a renal ostium than the
device 2600 of FIG. 26. The device 2700 includes a cooling assembly 2702
at a distal portion 2704 of an elongated shaft 2706 defining an exhaust
passage. The distal portion 2704 can have a step 2707, and the cooling
assembly 2702 can include an applicator 2708 with a balloon 2710 that
defines an expansion chamber and has proximal branches 2711, a tubular
main portion 2712, distal branches 2713, a plurality of recesses 2714,
and a non-recessed portion 2716. The plurality of recesses 2714 can be
arranged in a helical pattern around the circumference of the balloon
2710. When the cooling assembly 2702 is in a deployed state, the recesses
2714 and the non-recessed portion 2716 can function similarly to the
recesses 2612 and the non-recessed portion 2613 of the device 2600 shown
in FIG. 26. The proximal branches 2711 can be configured to fluidly
connect the tubular main portion 2712 to the exhaust passage. The device
2700 can further include an elongated guide member 2718 that can extend
along the length of the shaft 2706 and attach to the distal branches
2713, as well as a supply tube 2720 that extends along the length of the
shaft 2706, through one of the proximal branches 2711, and into the
tubular main portion 2712. The proximal branches 2711 and the distal
branches 2713 can be configured to space apart the tubular main portion
2712 from the guide member 2718. The cooling assembly 2702 can further
include an orifice 2722 at the distal end of the supply tube 2720.

[0219] When the cooling assembly 2702 is in a deployed state, the cooling
assembly 2702 can define a flow path (e.g., a blood flow path) between an
outside surface of the guide member 2718 and the balloon 2710. The flow
path can extend, for example, around the proximal branches 2711, through
the tubular main portion 2712 (e.g., between the guide member 2718 and an
inner surface of the tubular main portion 2712), and around the distal
branches 2713. As shown in FIG. 27B, the tubular main portion 2712 can
include a thermally-insulative inner portion 2724 around the flow path.
The thermally-insulative inner portion 2724 can be configured to at least
partially insulate fluid in the flow path from cryogenic cooling within
the tubular main portion 2712. In the illustrated embodiment, the
thermally-insulative inner portion 2724 can be a portion of the balloon
2710 having a greater thickness than other portions of the balloon 2710.
In several other embodiments, the thermally-insulative inner portion 2724
has a different composition from other portions of the balloon 2710
and/or includes one or more separate thermally-insulative structures.
Alternatively, the balloon 2710 can include a tubular main portion 2712
with an inner portion that is not more thermally insulative than other
portions of the balloon 2710.

[0220] FIG. 28 illustrates a portion of a cryotherapeutic device 2800
similar to the device 2600 of FIG. 26 except with regard to a
configuration of recessed and non-recessed portions. The device 2800
includes a cooling assembly 2802 having an applicator 2804 with a balloon
2806 that can define an expansion chamber. The balloon 2806 includes a
plurality of protrusions 2808 and a non-protruding portion 2810. The
protrusions 2808 can be arranged in a helical pattern or other suitable
pattern around the circumference of the balloon 2806. When the cooling
assembly 2802 is in a delivery state, the non-protruding portion 2810 can
correspond to a heat-transfer portion of the applicator 2804 having a
lower heat-transfer rate than portions of the applicator at the
protrusions 2808. The space between the non-protruding portion 2810 and
an inner surface of a renal artery or a renal ostium at a treatment site
can thermally insulate portions of the renal artery or the renal ostium
closest to the non-protruding portion from cryogenic temperatures within
the balloon 2806. For example, frozen or liquid blood within this space
can provide thermally insulation.

[0221] Balloons having different shapes can facilitate certain treatment
objectives related to cryogenic renal-nerve modulation. For example,
helical shapes can facilitate a desirable localized or overall treatment
pattern. FIG. 29 illustrates a portion of a cryotherapeutic device 2900
including a cooling assembly 2902 at a distal portion 2904 of an
elongated shaft 2906 defining an exhaust passage. The distal portion 2904
can have a step 2907, an exit hole 2908, and an exhaust port 2909. The
cooling assembly 2902 can include an applicator 2910 with a helical
balloon 2911 that defines an expansion chamber and has a balloon proximal
portion 2912 and a balloon distal portion 2914. The balloon proximal
portion 2912 has minor fluid connection with the exhaust passage through
the exit hole 2908. The balloon distal portion 2914 is attached to the
outside surface of the distal portion 2904 around the exhaust opening
2909, thereby fluidly connecting the helical balloon 2911 to the exhaust
passage. The helical balloon 2911 is wrapped around the distal portion
2904 (e.g., the distal portion 2904 can define a central axis of the
helical balloon 2911). The device 2900 can further include a supply tube
2916 defining a supply lumen and having a main portion 2918 extending
along the length of the shaft 2906 and an angled distal portion 2920
exiting the shaft 2906 through the exit hole 2908. The cooling assembly
2902 also can include an orifice 2922 at the distal end of the angled
distal portion 2920. The supply tube 2916 and the orifice 2922 can be
configured to direct expansion of refrigerant into the balloon proximal
portion 2912 in a direction generally corresponding to a longitudinal
orientation of the balloon proximal portion 2912. When the cooling
assembly 2902 is in a deployed state, refrigerant can flow from the
balloon proximal portion 2912 to the balloon distal portion 2914 and then
proximally along the exhaust passage. Upon reaching the balloon distal
portion 2914, the refrigerant can have exhausted some, most, or all of
its capacity for cryogenic cooling.

[0222]FIG. 30 illustrates a portion of a cryotherapeutic device 3000 that
differs from the device 2900 of FIG. 29 primarily with respect to a
refrigerant flow direction. The device 3000 includes a cooling assembly
3002 at a distal portion 3004 of an elongated shaft 3006 defining an
exhaust passage. The distal portion 3004 can have a step 3007, and the
cooling assembly 3002 can include an applicator 3008 having a helical
balloon 3014 that defines an expansion chamber and has a balloon proximal
portion 3016 and a balloon distal portion 3018. The balloon proximal
portion 3016 can be attached to an outside surface of the distal portion
3004 proximate a distal end of the distal portion 3004, thereby fluidly
connecting the helical balloon 3014 to the exhaust passage. The device
3000 can further include a supply tube 3019 having a curved distal
portion 3020. The helical balloon 3014 can be wrapped around the supply
tube 3019 (e.g., the supply tube 3019 can define a central axis of the
helical balloon 3014). The supply tube 3019 can extend along the length
of the shaft 3006, out of the shaft, out of the balloon proximal portion
3016, along a central axis of the helical balloon 3014, and into the
balloon distal portion 3018. The balloon distal portion 3016 can be
sealed around the supply tube 3019 and at least partially attached to the
curved distal portion 3020. The cooling assembly 3002 can further include
an orifice 3021 fluidly connecting the supply tube 3019 to the balloon
distal portion 3018. The supply tube 3019 and the orifice 3021 can be
configured to direct expansion of refrigerant into the balloon distal
portion 3018 in a direction generally corresponding to a longitudinal
orientation of the balloon distal portion 3018. When the cooling assembly
3002 is in a deployed state, refrigerant can flow from the balloon distal
portion 3018 to the balloon proximal portion 3016 and then proximally
along the exhaust passage.

[0223]FIG. 31 illustrates a portion of a cryotherapeutic device 3100
similar to the device 3000 of FIG. 30 except with regard to a helical
balloon shape. The device 3100 includes a cooling assembly 3102 at a
distal portion 3104 of an elongated shaft 3106 defining an exhaust
passage. The distal portion 3104 can have a step 3108, and the cooling
assembly 3102 can include an applicator 3110 having a helical balloon
3112 that defines an expansion chamber and has a balloon proximal portion
3114 and a balloon distal portion 3116. The balloon proximal portion 3114
can be attached to an outside surface of the distal portion 3104
proximate a distal end of the distal portion 3104, thereby fluidly
connecting the helical balloon 3112 to the exhaust passage. The device
3100 can further include a supply tube 3117 having an angled distal
portion 3118 The helical balloon 3112 can be wrapped around the supply
tube 3117 but also radially spaced apart from the supply tube 3117. The
supply tube 3117 can extend along the length of the shaft 3106, out of
the shaft 3106, out of the balloon proximal portion 3114, along a central
axis of the helical balloon 3112, and into the balloon distal portion
3116. The balloon distal portion 3116 can be sealed around the supply
tube 3117. The cooling assembly can further include an orifice 3119
fluidly connecting the supply tube 3117 to the balloon distal portion
3116. When the cooling assembly 3102 is in a deployed state, refrigerant
can flow from the balloon distal portion 3116 to the balloon proximal
portion 3114 and then proximally along the exhaust passage. The wide
helical diameter of the helical balloon 3112 can facilitate partial
occlusion. For example, when the cooling assembly 3102 is in the deployed
state, the cooling assembly 3102 can define a flow path (e.g., a blood
flow path) between an outside surface of the supply tube 3117 and the
helical balloon 3112.

[0224] FIGS. 32A-32B illustrate a portion of a cryotherapeutic device 3200
that can have a complex shape corresponding to a shaping member, such as
a shaping member having a shape memory. As discussed above, balloons in
cryotherapeutic devices configured in accordance with several embodiments
of the present technology can move from being at least partially
collapsed when a corresponding cooling assembly is in a delivery state,
to being at least partially expanded when the cooling assembly is in a
deployed state. When expanded in the deployed state, complex balloons can
have pre-defined shapes (e.g., integral shapes molded or otherwise
incorporated into the balloon) or shapes corresponding to separate
shaping structures. The cryotherapeutic device 3200 shown in FIGS.
32A-32B includes a cooling assembly 3202 at a distal portion 3204 of an
elongated shaft 3206 defining an exhaust passage. The distal portion 3204
can have a step 3207, and the cooling assembly 3202 can include an
applicator 3208. The device 3200 can further include an elongated shaping
member 3210 and a supply tube 3212 having an angled distal portion 3214.
The applicator 3208 can include a balloon 3216 with a distal seal 3217.
The balloon 3216 can extend around the elongated shaping member 3210 and
can define an expansion chamber. The distal seal 3217 can be a flattened
portion of the balloon 3216 at which walls of the balloon 3216 are sealed
together (e.g., thermally and/or with adhesive). Balloons configured in
accordance with several other embodiments of the present technology can
have another type of closed distal end. As discussed above, balloons can
be closed around structures, such as guide members and/or supply tubes.
Balloons also can be closed around plugs. Furthermore, balloons can have
integral closed distal ends. For example, balloons can be molded (e.g.,
dip molded) with integral closed distal ends.

[0225] The shaping member 3210 can be configured to have a generally
linear configuration when the cooling assembly 3202 is in a delivery
state and a curvilinear configuration when the cooling assembly 3202 is
in a deployed state. The cooling assembly 3202 can also include an
orifice 3218 at the distal end of the angled distal portion 3214. The
supply tube 3212 and the orifice 3218 can be configured to direct
expansion of refrigerant into the balloon 3216 in a direction generally
corresponding to a longitudinal orientation of the balloon 3216 proximate
the orifice 3218. As shown in FIG. 32A, the balloon 3216 has a shape in
the deployed state at least partially corresponding to the curvilinear
configuration of the shaping member 3210. The illustrated curvilinear
configuration is generally helical, but also could be another shape, such
as a serpentine shape. The shaping member 3210 can have a shape memory
(e.g., a one-way shape memory or a two-way shape memory) and can include
a shape-memory material, such as a nickel-titanium alloy (e.g., nitinol).
Shape memory can allow the shaping member 3210 and the balloon 3216 to
move into a pre-selected configuration (e.g., a curved, curvilinear,
helical, or serpentine configuration) in the deployed state. The
configuration can be selected, for example, to allow the applicator 3208
to apply a desirable localized or overall treatment pattern. Similarly,
the helical shape shown in FIG. 32A and other shapes can be selected to
provide a level of occlusion at a treatment site, such as partial
occlusion instead of full occlusion. Shape-memory materials can lose some
or all of their shaping properties when exposed to cryogenic
temperatures. Cooling assemblies 3202 configured in accordance with
several embodiments of the present technology can include balloons 3216
that move into a pre-selected configuration corresponding to a shape of a
shaping member 3210 before cryogenic cooling or during initial cryogenic
cooling. When the cryogenic cooling causes the shaping member 3210 to
lose some or all of its shaping properties, cryo-adhesion between the
balloon 3216 and external material (e.g., blood and/or tissue) can cause
the balloon 3216 to maintain its pre-selected configuration at least
until the cryo-adhesion ends.

[0226] In the embodiment illustrated in FIGS. 32A-32B, the shaping member
3210 is shown generally centered within the balloon, i.e., the balloon
3216 is generally uniformly expanded around the shaping member 3210.
Alternatively, the shaping member 3210 can have a different position
within the balloon 3216 when the cooling assembly 3202 is in the deployed
state. For example, the shaping member 3210 can be near an inner surface
of the balloon 3216. When the shaping member 3210 is spaced apart from
walls of the balloon 3216, the balloon 3216 can dissipate pressure
against a renal artery or renal ostium. As shown in FIG. 32A, the shaping
member 3210 can extend through the distal seal 3217. Alternatively, the
shaping member 3210 can be not attached to the balloon 3216 and/or
terminate at a portion of the balloon 3216 proximal to the distal seal
3217. Furthermore, a distal portion of the shaping member 3210 can be
configured to be spaced apart from a renal artery or renal ostium when
the cooling assembly 3202 is in the deployed state. In some embodiments,
the balloon 3216 is configured to generally uniformly expand around the
shaping member 3210 without any internal support structures.
Alternatively, the balloon 3216 can include an internal structure (e.g.,
webbing) extending across an inner diameter of the balloon 3216 and the
shaping member 3210 can be attached to the internal structure at a
position spaced apart from inner surfaces of the balloon 3216. The
internal structure, for example, can be a partition between separate
balloons (e.g., as discussed below with reference to FIGS. 45A-46). In
some embodiments, the cooling assembly includes a structure extending
along a central axis of the balloon 3216 in the deployed state. For
example, the distal portion 3204 can extend along the central axis of the
balloon 3216 in the deployed state and the balloon 3216 and the shaping
member 3210 can connect to a lateral opening of the distal portion 3204.
As another example, the distal portion 3204 can include a
reduced-diameter extension extending along the central axis of the
balloon 3216 and another opening separate from the reduced-diameter
extension fluidly connecting the balloon 3216 to the exhaust passage. A
structure extending along the central axis of the balloon 3216 can
include a lumen (e.g., a lumen configured to receive a guide wire or a
control wire), a protection device (e.g., a filter), and/or a monitoring
device (e.g., a thermocouple or a pressure transducer).

[0227] The device 3200 can be modified for use in non-cryotherapeutic
applications. For example, the supply tube 3212 can be removed and the
device 3200 can be used in other applications that benefit from less than
full occlusion at a treatment site. In both renal-neuromodulation
applications and other applications, the balloon 3216 can be
non-occlusive in the deployed state, e.g., a blood flow path can be
formed along a central axis of the balloon 3216. In some
non-cryotherapeutic applications, the distal portion 3204 can support a
structure configured to execute a treatment (e.g., a thrombectomy) within
a vessel while the balloon 3216 anchors the device 3200 to a vessel wall.
In these and other embodiments, the balloon 3216 advantageously can
maintain the distal portion 3204 at a central position within a vessel.

[0228] FIGS. 33A-33D illustrate a portion of a cryotherapeutic device 3300
that can have a pre-defined curved shape in a deployed configuration. The
device 3300 includes a cooling assembly 3302 at a distal portion 3304 of
an elongated shaft 3306 defining an exhaust passage. The distal portion
3304 can have a step 3307, and the cooling assembly 3302 can include an
applicator 3308 with a balloon 3310 that can define an expansion chamber.
The balloon 3310 can have a balloon proximal portion 3312, a balloon
middle portion 3314, and a balloon distal portion 3316. The device 3300
further includes a supply tube 3318 extending along the shaft 3306, and
the cooling assembly 3302 can have an orifice 3320 at the distal end of
the supply tube 3318 and within the balloon proximal portion 3312. When
the cooling assembly 3302 is in a deployed state, the balloon 3310 is
curved along its length and has a generally concave first wall 3322
(shown as a lower portion of the balloon in FIG. 33A) and a generally
non-concave (e.g., convex) second wall 3324 (shown as an upper portion of
the balloon in FIG. 33A).

[0229] The balloon proximal portion 3312, the balloon middle portion 3314,
and the balloon distal portion 3316 can be configured to contact
partially circumferential portions of a renal artery or a renal ostium.
For example, the balloon middle portion 3314 can be configured to contact
a renal artery or a renal ostium generally along the second wall 3324 and
generally not along the first wall 3322 when the cooling assembly 3302 is
in a deployed state. The balloon proximal portion 3312 and the balloon
distal portion 3316, for example, can be configured to contact a renal
artery or a renal ostium generally along the first wall 3322 and
generally not along the second wall 3324 when the cooling assembly 3302
is in the deployed state. Due to this uneven pattern of contact, the
curved shape of the balloon 3310 can facilitate a desirable localized or
overall treatment pattern.

[0230] As best seen in FIGS. 33B-33C, the balloon 3310 can include a
reduced-elasticity portion 3326 along the first wall 3322 at the balloon
middle portion 3314. In the illustrated embodiment, the
reduced-elasticity portion 3326 can be a thicker portion of the balloon
3310. As shown in FIG. 33D, the balloon 3310 can be partially collapsed
when the cooling assembly 3302 is in the delivery state so as to fit
within a delivery sheath 3328. When the cooling assembly 3302 is in the
delivery state, the reduced-elasticity portion 3326 can retain some
curvature. Alternatively, the reduced-elasticity portion 3326 can be
generally flat. When the cooling assembly 3302 is in a deployed state,
portions of the balloon 3310 other than the reduced elasticity portion
3326, particularly portions of the balloon 3310 along the second wall
3324 at the balloon middle portion 3314 can be configured to expand
(e.g., compliantly expand) to a greater degree than the
reduced-elasticity portion 3326. In several embodiments, the
reduced-elasticity portion 3326 is generally non-compliant and a portion
of the balloon 3310 along the second wall 3324 at the balloon middle
portion 3314 is generally compliant. Restriction associated with the
reduced-elasticity portion 3326 can facilitate curvature of the balloon
3310 when the cooling assembly 3302 is in the deployed state. The
reduced-elasticity portion 3326 can be configured to be recessed relative
to a renal artery or a renal ostium when the cooling assembly 3302 is in
the deployed state and, correspondingly, not encompass a heat-transfer
portion having a heat-transfer rate sufficient to cause
therapeutically-effective renal nerve modulation. In addition to reducing
elasticity, the thickness of the reduced-elasticity portion 3326 can
reduce its thermal conductivity, which can promote improve cooling
efficiency and/or further facilitate a desirable localized or overall
treatment pattern.

[0231]FIG. 34 illustrates a portion of a cryotherapeutic device 3400
similar to the device 3300 of FIGS. 33A-33D except having a different
support configuration. The device 3400 includes a cooling assembly 3402
having an applicator 3404 with a balloon 3406 defining an expansion
chamber. The cooling assembly 3402 also includes an elongated support
member 3408 having a curved distal end 3410. The elongated support member
3408 and other support members described herein can help balloons move
with a corresponding cooling assembly as the cooling assembly moves
between a delivery state and a deployed state. For example, the elongated
support member 3408 can help to prevent the balloon 3406 from becoming
stuck or twisted during treatment. Optionally, elongated support members
can be attached to distal portions of corresponding balloons. This can be
useful, for example, to maintain a balloon in an elongated configuration.

[0232] FIGS. 35A-35B illustrate a portion of a cryotherapeutic device 3500
in which interaction with a guide member at least partially causes a
complex balloon shape. In several other embodiments, a complex balloon is
at least partially shaped through interaction with another
cryotherapeutic-device component (e.g., a shaft or a supply tube). The
device 3500 shown in FIGS. 35A-35B includes a cooling assembly 3502 at a
distal portion 3504 of an elongated shaft 3506 defining an exhaust
passage. The device 3500 can include an elongated guide member 3508 and a
supply tube 3512, and the cooling assembly 3502 can include an orifice
3514 at the distal end of the supply tube 3512. The cooling assembly can
further include an applicator 3510 with a balloon 3516 that can define an
expansion chamber and can have a balloon proximal portion 3518, a
proximal integral neck 3520 attached to the distal portion 3504, and a
distal integral neck 3522 attached to the guide member 3508. The balloon
3516 can also have a constrained longitudinal portion 3524 (FIG. 35B) and
an expandable longitudinal portion 3526 (FIG. 35B). The constrained
longitudinal portion 3524 can be at least partially attached to the guide
member 3508. For example, from the distal integral neck 3522 to the
balloon proximal portion 3518, an internal surface of the balloon 3516
can be attached to the guide member 3508. The expandable longitudinal
portion 3526 can be spaced apart from the guide member 3508 when the
cooling assembly 3502 is in a deployed state. The partially-constrained
shape of the balloon 3516 can be useful to facilitate a desirable
localized or overall treatment pattern. Furthermore, the constrained
longitudinal portion 3524 can define at least a portion of a longitudinal
flow path (e.g., a blood flow path) around the balloon 3516. This can be
useful, for example, to facilitate a level of occlusion at a treatment
site, such as partial occlusion instead of full occlusion.

[0233]FIG. 36 illustrates a cryotherapeutic device 3600 similar to the
cryotherapeutic device 3500 of FIGS. 35A-35B, except having a different
pattern of attachment between a balloon and a guide member. FIG. 36 can
be considered as a substitute for FIG. 35B to illustrate a separate
embodiment in which all elements of the cryotherapeutic device 3500 shown
in FIGS. 35A-35B are similar except for those shown differently in FIG.
36 relative to FIG. 35B. The cryotherapeutic device 3600 includes an
elongated guide member 3602 and a balloon 3604 having radially spaced
apart constrained longitudinal portions 3506 and radially spaced apart
expanded longitudinal portions 3508. Although FIG. 36 shows two
constrained longitudinal portions 3606 and two expanded longitudinal
portions 3608, a greater number of constrained longitudinal portions 3606
and/or expanded longitudinal portions 3608 can be formed for example, by
attaching the balloon 3604 to the guide member 3602 at a different number
of radial segments of the guide member 3602. Furthermore, the
distribution of constrained longitudinal portions 3606 and expanded
longitudinal portions 3608 can be symmetrical or asymmetrical (e.g.,
along an axis parallel to the length of the guide member 3602).

[0234]FIG. 37 illustrates a portion of a cryotherapeutic device 3700
including a balloon having a loop shape. The device 3700 includes a
cooling assembly 3702 at a distal portion 3704 of an elongated shaft 3706
defining an exhaust passage, as well as a supply tube 3708. The cooling
assembly 3702 includes an orifice 3710 at the distal end of the supply
tube 3708, and an applicator 3712 with a balloon 3714 having a first
balloon segment 3716 and a second balloon segment 3718. The first balloon
segment 3716 has a first proximal portion 3720 and a first distal portion
3722. The second balloon segment 3718 has a second proximal portion 3724
and a second distal portion 3726. The first balloon distal portion 3722
is fluidly connected to the second distal portion 3726. When the cooling
assembly 3702 is in the deployed state, refrigerant can flow from the
first proximal portion 3720, to the first distal portion 3722, and then
to the second distal portion 3726. Upon reaching the second distal
portion 3726, the refrigerant can have exhausted some, most, or all of
its capacity for cryogenic cooling. Accordingly, the second balloon
segment 3718 can serve primarily to exhaust refrigerant from the first
distal portion 3722 and have a heat-transfer portion with a heat-transfer
rate lower than a heat-transfer rate of a heat-transfer portion of the
first balloon-segment 3716. In several alternative embodiments, the first
balloon segment 3716 and the second balloon segment 3718 are separate
balloons with a fluid connection at their distal ends. In another
embodiment, the first and second balloon segments can be portions of a
single balloon that is folded. Similar to non-cooling balloons discussed
below, the second balloon segment 3718 can thermally insulate a portion
of a renal artery or a renal ostium at a treatment site from cryogenic
temperatures within the first balloon segment 3716. This can be useful,
for example, to facilitate a desirable localized or overall treatment
pattern.

Multiple Balloons

[0235] FIGS. 38-51 illustrate several embodiments of cryotherapeutic
devices that include multiple balloons that can facilitate one or more
treatment objectives related to cryogenic renal-nerve modulation, such as
a desirable localized or overall treatment pattern, sizing, and full
occlusion. In cryotherapeutic devices configured in accordance with
several embodiments of the present technology, a primary balloon
configured to generate or deliver therapeutically effective cooling for
renal nerve modulation (e.g., including a primary heat-transfer portion)
can be used in conjunction with a secondary balloon configured to prevent
or inhibit therapeutically effective cooling temperatures at selected
locations. In several embodiments, a secondary balloon includes a
secondary heat-transfer portion. A secondary balloon, for example, can be
warming, thermally-insulative, non-cooling, or have a low-level of
cooling. Alternatively, several embodiments include multiple balloons
that include primary heat-transfer portions with or without a secondary
balloon.

[0236] FIGS. 38A-38B illustrate a portion of a cryotherapeutic device 3800
that can have multiple primary balloons. The device 3800 includes a
cooling assembly 3802 at a distal portion 3804 of an elongated shaft 3806
defining an exhaust passage. The distal portion 3804 can have a step
3807, and the device 3800 can include an elongated guide member 3808 and
a supply tube 3810. The cooling assembly 3802 can include an orifice 3811
at the distal end of the supply tube 3810 and an applicator 3812 having
elongated balloons 3814 positioned generally parallel to a length of the
cooling assembly 3802. The balloons 3814 have a shared proximal portion
3816 and are otherwise circumferentially distributed around the guide
member 3808. The orifice 3811 is within the shared proximal portion 3816
and the balloons 3814, in conjunction with the shared proximal portion
3816, can define expansion chambers. When the cooling assembly 3802 is in
a deployed state, refrigerant expanded from the supply tube 3810 can
enter the shared proximal portion 3816 and circulate within the balloons
3814 to cause expansion thereof and cooling. Refrigerant can exit the
balloons 3814 also through the shared proximal portion 3816 and flow
proximally along the exhaust passage. The balloons 3814 can be configured
to contact spaced-apart portions (e.g., spaced-apart longitudinal
portions) of a renal artery or a renal ostium at a treatment site. This
can be useful to facilitate a desirable localized or overall treatment
pattern. Furthermore, space between the balloons 3814 can define at least
a portion of a longitudinal flow path (e.g., a blood flow path) around
the balloons 3814. This can be useful, for example, to facilitate a level
of occlusion at a treatment site, such as partial occlusion instead of
full occlusion.

[0237] FIGS. 39A-39C illustrate a portion of a cryotherapeutic device 3900
that can have multiple balloons having different levels of cooling. The
device 3900 includes a cooling assembly 3902 at a distal portion 3904 of
an elongated shaft 3906, an elongated guide member 3907, and a plurality
of supply tubes (individually identified as 3908a-d). The cooling
assembly 3902 can include a plurality of orifices (individually
identified as 3910a-d) at the distal ends of the supply tubes 3908a-d,
and an applicator 3912 including a plurality of elongated balloons
(individually identified as 3914a-d in FIGS. 39A and 39C). The balloons
3914a-d are circumferentially distributed around the guide member 3907
and individually include proximal necks 3916 (FIG. 39A) that can fluidly
connect the balloons 3914a-d to the exhaust passage. The orifices 3910a,
3910d have larger free-passage areas than the orifices 3910b, 3910c.
Similarly, the supply tubes 3908a, 3908d have smaller free-passage areas
than the supply tubes 3908b, 3908d. The balloons 3914a-d are generally
equal in size and have generally equal internal and external surface
areas. A ratio of orifice and/or supply tube free-passage area to
internal surface area can be greater for the balloons 3914a, 3914d than
for the balloons 3914b, 3914c. This can cause differential cooling within
the balloons 3914a, 3914d relative to the balloons 3914b, 3914c. For
example, the balloons 3914a, 3914d can be configured to circulate gaseous
refrigerant at a lower temperature than the balloons 3914b, 3914c. In
addition or alternatively, the balloons 3914a, 3914d can be configured
for generally surface-area limited cooling when the cooling assembly 3902
is in the deployed state, while the balloons 3914b, 3914c are configured
for generally refrigerant-limited cooling when the cooling assembly 3902
is in the deployed state. Providing some cooling (e.g., low-level
cooling, such as cooling insufficient for cryogenic renal nerve
modulation) to tissue near an area targeted for therapeutically-effective
renal nerve modulation can be useful, for example, to reduce heat-gain
from surrounding tissue at the area targeted for
therapeutically-effective renal nerve modulation. The use of multiple
balloons also can facilitate a desirable localized or overall treatment
pattern and/or a desired level of occlusion at a treatment site, such as
partial occlusion instead of full occlusion.

[0238]FIG. 40 illustrates a cryotherapeutic device 4000 similar to the
cryotherapeutic device 3900 of FIGS. 39A-39C, except having a different
mechanism for differential cooling. FIG. 40 can be considered as a
substitute for FIG. 39B to illustrate a separate embodiment in which all
elements of the cryotherapeutic device 3900 shown in FIGS. 39A-39C are
similar except for those shown differently in FIG. 40 relative to FIG.
39B. The cryotherapeutic device 4000 includes a shaft 4002 having
internal walls 4004 dividing the shaft 4002 into fluidly separate exhaust
passages, and supply tubes 4006 individually within the exhaust passages.
The supply tubes 4006 have generally equal sizes and can have orifices
(not shown) having generally equal sizes. The cryotherapeutic device 4000
also includes a plurality of pressure regulators (individually identified
as 4008a-d) in fluid communication with the exhaust passages. The
pressure regulators 4008a-d can be configured to be positioned outside
the vasculature. Regulating back pressures within the exhaust passages
can cause temperatures within corresponding balloons (not shown) to vary.
For example, the pressure regulators 4008a, 4008d can maintain a first
back pressure in the corresponding exhaust passages and balloons, and the
pressure regulators 4008b, 4008c can maintain a second, different back
pressure in the corresponding exhaust passages and balloons. In this way,
differential cooling similar to the differential cooling described above
with reference to the device 3900 shown in FIGS. 39A-39C can be achieved.

[0239] FIG. 41 illustrates a portion of a cryotherapeutic device 4100 that
can have multiple helical balloons. The device 4100 includes a cooling
assembly 4101 at a distal portion 4102 of an elongated shaft 4103
defining an exhaust passage, a supply tube 4104, and a filler tube 4105.
The cooling assembly 4101 can include a first supply orifice 4106, a
second supply orifice 4107, and a filler orifice 4108 at the distal end
of the filler tube 4105. The cooling assembly 4101 also includes an
applicator 4109 having a plurality of helical balloons. In one
embodiment, the applicator 4109 includes a first helical balloon 4110
having a first distal portion 4112 and a first proximal portion 4114, a
second helical balloon 4116 (shown stippled for clarity of illustration)
having a second distal portion 4118 and a second proximal portion 4120,
and a third helical balloon 4122 having a third distal portion 4124 and a
third proximal portion 4126. The first and second supply orifices 4106,
4107 can be fluidly connected to the first distal portion 4112 and the
third distal portion 4124, respectively, and the first and third helical
balloons 4110, 4122 can define expansion chambers. The second-balloon
proximal portion 4120 can be sealed around the filler tube 4107 and
fluidly connected to the filler orifice 4108 and the second helical
balloon 4116 can define a filler chamber. When the cooling assembly 4101
is in the deployed state, the second helical balloon 4116 can be
configured to be filled via the filler tube 4105. Refrigerant can expand
into the first distal portion 4112 and the third distal portion 4124, and
the first and third helical balloons 4110, 4122 can provide primary
cooling in separate helical patterns or a combined helical pattern. The
second helical balloon 4116 can thermally insulate portions of a renal
artery or a renal ostium from cryogenic cooling of the first and third
helical balloons 4110, 4122. This can be useful, for example, to
facilitate a desirable localized or overall treatment pattern.
Furthermore, the interior space between the supply tube 4004 and the
first, second, and third helical balloons 4110, 4116, 4122 can define at
least a portion of a longitudinal flow path (e.g., a blood flow path).
This can be useful, for example, to facilitate a level of occlusion at a
treatment site, such as partial occlusion instead of full occlusion.

[0240]FIG. 42 illustrates a portion of a cryotherapeutic device 4200
similar to the device 4100 shown in FIG. 41, but having modified supply
and exhaust configurations in the helical balloons. The device 4200
includes a cooling assembly 4202 at a distal portion 4203 of an elongated
shaft 4204 defining an exhaust passage, an elongated guide member 4205,
and a supply tube 4206. The cooling assembly 4202 can include a supply
orifice 4207 at the distal end of the supply tube 4206 and an applicator
4208 having a plurality of helical balloons. In one embodiment, the
applicator 4208 includes a first helical balloon 4210 having a first
distal portion 4212 and a first proximal portion 4214, a second helical
balloon 4216 (shown stippled for clarity of illustration) having a second
distal portion 4218 and a second proximal portion 4220, and a third
helical balloon 4222 having a third distal portion 4224 and a third
proximal portion 4226. The first distal portion 4212 and the third distal
portion 4224 are fluidly connected to each other and to the second distal
portion 4218. The first proximal portion 4214 and the third proximal
portion 4226 are fluidly connected to the exhaust passage. When the
cooling assembly 4202 is in the deployed state, refrigerant can expand
into the second proximal portion 4220 and the second helical balloon 4216
can provide primary cooling in a helical pattern. The first and third
helical balloons 4210, 4222 can receive refrigerant exhaust from the
second distal portion 4218 and can thermally insulate portions of a renal
artery or a renal ostium from cryogenic cooling within the second helical
balloon 4216. Relative to the cryotherapeutic device 4200 shown in FIG.
41, the device 4100 can be useful when less cooling and/or greater
spacing between areas of primary cooling is desirable. In several other
embodiments, different numbers of helical balloons that are warming,
thermally-insulative, non-cooling, or have a low-level of cooling are
intertwined in various arrangements with helical balloons configured to
provide primary cooling, such as to facilitate a desirable localized or
overall treatment pattern.

[0241] FIGS. 43A-43C illustrate a portion of a cryotherapeutic device 4300
that can include balloons that are movable relative to other portions of
a cooling assembly. The device 4300 includes a cooling assembly 4301 at a
distal portion 4302 of an elongated shaft 4303 defining an exhaust
passage, as well as an elongated shaping member 4304, a first supply tube
4305, and a second supply tube 4306. The distal portion 4302 can have a
step 4307, and the cooling assembly 4301 can include a first orifice 4308
at the distal end of the first supply tube 4305, and a second orifice
4309 at the distal end of the second supply tube 4306. The cooling
assembly 4301 further includes an applicator 4310 with a first elongated
balloon 4311 defining a first expansion chamber and a second elongated
balloon 4312 defining a second expansion chamber. The first balloon 4311
has a first proximal portion 4314, a first middle portion 4315, and a
first distal portion 4316. The second balloon 4312 has a second proximal
portion 4318, a second middle portion 4319, and a second distal portion
4320. The first and second balloons 4311, 4312 have inner sides 4322
closest to the shaping member 4304 and outer sides 4324 opposite the
inner sides 4322. The first distal portion 4316 and the second distal
portion 4320 are attached to the shaping member 4304. In several
embodiments, the shaping member 4304 also defines a guide lumen through
which a guide wire can be threaded.

[0242] As shown in FIG. 43C, when the cooling assembly 4301 is in the
deployed state, retracting the shaping member 4304 relative to the shaft
4303 can cause the first middle portion 4315 and the second middle
portion 4319 to laterally move away from the shaping member 4304. A
portion of the first middle portion 4315 and/or a portion of the second
middle portion 4319 can be weakened (e.g., creased, heat-treated to cause
weakening, and/or thinned) or otherwise configured to define a
preferential bend position. As shown in FIG. 43C, after the shaping
member 4304 has retracted the inner sides 4322 of the first middle
portion 4315 and the second middle portion 4319 are generally concave
along their lengths, while the outer sides 4324 of the first middle
portion 4315 and the second middle portion 4319 are generally convex
along their lengths. Controlled deflection of balloons can be
particularly useful, for example, to facilitate sizing with low risk of
applying excessive expansive pressure to a renal artery or a renal
ostium. Controlled deflection can be particularly useful when one or more
balloons of an applicator are generally non-compliant and/or achieving
sizing through compliant expansion is not practical.

[0243] FIGS. 44A-44C illustrate a portion of a cryotherapeutic device 4400
similar to the cryotherapeutic device 4300 shown in FIGS. 43A-43B, but
having a greater number of elongated balloons and including a secondary
balloon. The device 4400 includes a distal portion 4402 of an elongated
shaft 4404 having a step 4405 and defining an exhaust passage, a cooling
assembly 4406 at the distal portion 4402, and an elongated shaping member
4408. The shaping member 4304 can be solid or can define a lumen, such as
a guide lumen through which a guide wire can be threaded. The device 4400
further includes a first supply tube 4410, a second supply tube 4414, a
third supply tube (not shown), and a filler tube 4416. The cooling
assembly 4406 can include a first supply orifice 4418 at the distal end
of the first supply tube 4410, a second supply orifice 4420 at the distal
end of the second supply tube 4414, a third orifice (not shown) at the
distal end of the third supply tube, and a filler orifice 4422 at the
distal end of the filler tube 4416. The cooling assembly 4406 also
includes an applicator 4424 with an elongated first balloon 4426 defining
a first expansion chamber, an elongated second balloon 4428 defining a
second expansion chamber, an elongated third balloon 4430 (FIG. 44B)
defining a third expansion chamber, and an elongated fourth balloon 4432
defining a filler chamber. The first, second, and third balloons 4426,
4428, 4430 are fluidly connected to the first, second, and third supply
orifices 4418, 4420. The fourth balloon is fluidly connected to the
filler orifice 4422 and is sealed around the filler tube 4416. The first,
second, third, and fourth balloons 4426, 4428, 4430, 4432 are attached to
the shaping member 4408 such that, as shown in FIG. 44C, when the cooling
assembly 4406 is in a deployed state, retracting the shaping member 4408
relative to the shaft 4404 causes the applicator 4424 to laterally
expand. The first, second, and third balloons 4426, 4428, 4430 can have
heat-transfer portions with heat-transfer rates sufficient to cause
therapeutically-effective renal nerve modulation. The first, second, and
third balloons 4426, 4428, 4430 can be configured to provide primary
cooling. The fourth balloon 4432 can be a secondary balloon. In several
other embodiments, a different number of primary balloons with or without
secondary balloons can be included in a similar configuration to the
configurations of the cryotherapeutic device 4300 shown in FIGS. 43A-43B
and the cryotherapeutic device 4400 shown in FIGS. 44A-44C. In addition
to sizing, these configurations can facilitate other treatment
objectives, such as a desirable localized or overall treatment pattern

[0244] FIGS. 45A-45B illustrate a portion of a cryotherapeutic device 4500
including a primary balloon and a secondary balloon that can have
different compositions. The device 4500 includes a cooling assembly 4502
at a distal portion 4504 of an elongated shaft 4506 defining an exhaust
passage, a supply tube 4508, and a filler tube 4509. The cooling assembly
4502 includes a supply orifice 4510 at the distal end of the supply tube
4508, and a filler orifice 4514 at the distal end of the filler tube
4509. The cooling assembly 4502 also includes an applicator 4516 with a
first balloon 4518 that defines an expansion chamber and a second balloon
4520 that can define a filler chamber. The first balloon 4518 has a
proximal neck 4522 within the distal portion 4504 fluidly connecting the
first balloon 4518 to the exhaust passage. The second balloon is sealed
around the filler tube 4509 and fluidly connected to the filler orifice
4514. When the cooling assembly 4502 is in a deployed state, the first
balloon 4518 can be configured to deliver primary cooling and the second
balloon 4520 can be a secondary balloon.

[0245] In several embodiments, the first balloon 4518 has a lower level of
compliance and/or elasticity than the second balloon 4520. For example,
the first balloon 4518 can be generally non-compliant and the second
balloon can be generally compliant. Additionally, the first balloon 4518
can be non-compliant and the second balloon can be compliant.
Non-compliant materials typically have higher strength (e.g., higher
pressure ratings) than compliant materials. For this and/or other
reasons, generally compliant materials can be well suited for balloons
configured to receive expanded refrigerant directly from an orifice
and/or to apply therapeutically effective cooling for renal nerve
modulation. Generally compliant materials can be well suited for
expanding to different sizes to accommodate renal arteries and renal
ostiums having different cross-sectional dimensions. The device 4500
shown in FIGS. 45A-45B and several other cryotherapeutic-device
components described herein can be configured to take advantage of the
different properties of both non-compliant and compliant materials. FIGS.
45B and 45C are cross-sectional views of the device 4500 sized to fit
within renal arteries or renal ostiums of different cross-sectional
dimensions. The first balloon 4518 has generally the same size in both
FIG. 45B and FIG. 45C. The second balloon 4520, however, is compliantly
expanded to a greater degree in FIG. 45C than in FIG. 45B. Even with the
generally non-compliant expansion of the first balloon 4518, the
variable, compliant expansion of the second balloon 4520 can move the
first balloon into contact with an inner surface of a renal artery or a
renal ostium. Compliant expansion of the second balloon 4520 can be
carefully controlled via the filler tube 4509 to prevent excessive
expansive forces on the renal artery or the renal ostium.

[0246] The enlargement in FIG. 45B-1 shows a partition 4524 that includes
a layer of non-compliant material 4526 and a layer of compliant material
4528. The layer of non-compliant material 4526 can be a portion of the
first balloon 4518 and the layer of compliant material 4528 can be a
portion of the second balloon 4520. In one embodiment, the first balloon
4518 and the second balloon 4520 can be attached together at the
partition 4524, but in other embodiments the first and second balloon
4518 and 4520 are not attached to each other.

[0247]FIG. 46 illustrates a cryotherapeutic device 4600 similar to the
cryotherapeutic device 4500 of FIGS. 45A-45C, except having a different
partition. FIG. 46 can be considered as a substitute for FIG. 45B to
illustrate a separate embodiment in which all elements of the
cryotherapeutic device 4500 shown in FIGS. 45A-45C are similar except for
those shown differently in FIG. 46 relative to FIG. 45B. The
cryotherapeutic device 4600 includes a first balloon 4602, a second
balloon 4604, and a partition 4606 between the first balloon 4602 and the
second balloon 4604. As shown in the enlargement in FIG. 46-1, the
partition 4606 includes a single layer, which can be a non-compliant
layer of the first balloon. In another embodiment, the partition 4606 can
include a single layer that is a compliant layer of the second balloon
4604. To construct the device 4600, a generally compliant balloon portion
(e.g., an incomplete balloon) can be attached to a generally
non-compliant balloon so as to form a generally compliant balloon having
a chamber at least partially defined by a portion of the generally
non-compliant balloon. In cross section, as shown in FIG. 46, the first
balloon 4602 can be a generally D-shaped balloon and the second balloon
4604 can be a generally C-shaped balloon attached to a generally D-shaped
balloon.

[0248] Cryotherapeutic devices configured in accordance with several
embodiments of the present technology can include helical primary
balloons and non-helical secondary balloons. FIG. 47 illustrates a
portion of a cryotherapeutic device 4700 including a cooling assembly
4702 at a distal portion 4704 of an elongated shaft 4706 defining an
exhaust passage. The device 4700 also includes a supply tube 4707. The
cooling assembly 4702 includes an applicator 4708 with a helical first
balloon 4710 having a first proximal portion 4712 and a first distal
portion 4714 and defining an expansion chamber. The supply tube 4707 can
extend into the first proximal portion 4712, and the cooling assembly
4702 can have an orifice 4718 at the distal end of the supply tube 4707
within the first proximal portion 4712. The first proximal portion 4712
is sealed around the supply tube 4707. The cooling assembly 4702 can
further include a second balloon 4720 having a second proximal portion
4722 and a second distal portion 4724 and defining an exhaust chamber.
The second distal portion 4724 can be fluidly connected to the first
distal portion 4714, and the first balloon 4710 can wrap around the
second balloon 4720. The second proximal portion 4722 can be fluidly
connected to the exhaust passage. When the cooling assembly 4702 is in a
deployed state, refrigerant can flow from the first proximal portion 4712
to the first distal portion 4714 and then proximally through the second
balloon 4720. Back pressure from the refrigerant can cause the second
balloon 4720 to expand (e.g., compliantly expand), which can cause a
helical diameter of the first balloon 4710 to increase. This can be
useful, for example, to facilitate sizing. In addition, the helical shape
of the first balloon 4710 can be useful, for example, to facilitate a
desirable localized or overall treatment pattern.

[0249] FIGS. 48A-48B illustrate a portion of a cryotherapeutic device 4800
having a helical primary balloon and a non-helical secondary balloon in a
different configuration. The device 4800 includes a cooling assembly 4802
at a distal portion 4804 of an elongated shaft 4806 defining an exhaust
passage. The distal portion 4804 can have a step 4807, and the cooling
assembly 4802 can include an applicator 4808 with a helical first balloon
4810 that defines an expansion chamber and has a first proximal portion
4812 and a first distal portion 4814. The device 4800 also can include a
supply tube 4816 extending into the first proximal portion 4812, and the
cooling assembly 4802 can have an orifice 4818 at the distal end of the
supply tube 4816 within the first proximal portion 4812. The first
proximal portion 4812 is sealed around the supply tube 4816. The cooling
assembly 4802 can further include a second balloon 4820 having an
integral proximal neck 4822 attached to the distal portion 4804. The
second balloon 4820 can define an exhaust chamber configured to expand
(e.g., compliantly expand) in response to back pressure from refrigerant
exhausted from the first balloon 4810. The first balloon 4810 can be
attached to an internal surface of the second balloon 4820. Expansion
(e.g., compliant expansion) of the second balloon 4820 can cause a
helical diameter of the first balloon 4810 to increase, such as to move a
curved portion of the first balloon 4810 closer to an inner surface of a
renal artery or a renal ostium. Positioning the first balloon 4810 within
the second balloon 4820 can be useful, for example, to provide redundant
containment of refrigerant within the vasculature.

[0250]FIG. 49 illustrates a portion of a cryotherapeutic device 4900
including a helical primary balloon and a non-helical secondary balloon
in another configuration. The device 4900 includes a cooling assembly
4902 at a distal portion 4904 of an elongated shaft 4905 defining an
exhaust passage. The distal portion 4904 can have a step 4906 and a
plurality of exhaust openings 4907. The cooling assembly 4902 can include
an applicator 4908 with a helical first balloon 4910 that defines an
expansion chamber and has a first proximal portion 4912 and a first
distal portion 4914. The device 4900 also can include a supply tube 4916
that extends into the first proximal portion 4912, and the cooling
assembly 4902 can have an orifice 4918 at the distal end of the supply
tube 4916. The first proximal portion 4912 can be sealed around the
supply tube 4916. The cooling assembly 4902 can further include a second
balloon 4920 positioned around the distal portion 4904 and having an
integral proximal neck 4922 attached to the distal portion 4904. The
first balloon 4910 can wrap around the second balloon 4920 and the first
distal portion 4914 can be fluidly connected to the distal portion 4904
distal of the second balloon 4920. When the cooling assembly 4902 is in a
deployed state, the second balloon 4920 can be configured to passively
receive refrigerant from the exhaust passage through the exhaust openings
4907 and can be configured to expand (e.g., compliantly expand) in
response to back pressure from refrigerant exhausted from the first
balloon 4910. Expansion (e.g., compliant expansion) of the second balloon
4920 can cause a helical diameter of the first balloon 4910 to increase,
which can cause a portion (e.g., a curved portion) of the first balloon
4910 to move closer to an inner surface of a renal artery or a renal
ostium.

[0251]FIG. 50 illustrates a portion of a cryotherapeutic device 5000
including a helical primary balloon and a non-helical secondary balloon
in another configuration. The device 5000 includes a cooling assembly
5002 at a distal portion 5003 of an elongated shaft defining an exhaust
passage, a filler tube 5004, a filler orifice 5005 at the distal end of
the filler tube 5004, and a supply tube 5006. The cooling assembly 5002
includes a supply orifice 5007 at the distal end of the supply tube 5006.
The supply tube 5006 can include a corner 5008, such as an elbow, near
the supply orifice 5007. The cooling assembly 5002 further includes an
applicator 5009 with a helical first balloon 5010 that defines an
expansion chamber and has a first proximal portion 5011 and a first
distal portion 5012. The cooling assembly 5002 can also include a second
balloon 5014 having a second proximal portion 5016 and a second distal
portion 5018. The second proximal portion 5016 can be fluidly connected
to the filler orifice 5005 and sealed around the filler tube 5004. The
second distal portion 5018 can be sealed around the supply tube 5006, but
fluidly separate from the supply tube 5024 and the first balloon 5010.
The first balloon 5010 can wrap around the second balloon 5014 and be
configured to receive refrigerant from the supply tube 5006 and to
exhaust the refrigerant through the first proximal portion 5011 into the
exhaust passage. The second balloon 5014 can be configured to receive
filler material from the filler tube 5004 and expand (e.g., compliantly
expand) causing a helical diameter of the first balloon 5010 to increase,
which can cause a portion (e.g., a curved portion) of the first balloon
5010 to move closer to an inner surface of a renal artery or a renal
ostium.

[0252]FIG. 51 illustrates a portion of a cryotherapeutic device 5100
including a helical primary balloon and a non-helical secondary balloon
in another configuration. The device 5100 includes a cooling assembly
5101 at a distal portion 5102 of an elongated shaft 5103 defining an
exhaust passage, a supply tube 5106, and a filler tube 5108. The distal
portion 5102 can have a step 5104 and an exit hole 5105. The cooling
assembly 5101 can include a supply orifice 5107 at the distal end of the
supply tube 5106, and a filler orifice 5109 at the distal end of the
filler tube 5108. The cooling assembly 5101 can further include an
applicator 5110 with a helical first balloon 5111 that defines an
expansion chamber and has a first proximal portion 5112 and a first
distal portion 5114. The supply tube 5106 can extend from the exit hole
5105 and extend into the first proximal portion 5112, and the first
proximal portion 5112 can be sealed around the supply tube 5106. The
cooling assembly 5101 can further include a second balloon 5116 around
the distal portion 5102 and having an integral proximal neck 5118
attached to the distal portion 5102. The second balloon 5116 can be
configured to receive filler material from the filler tube 5108 and
expand (e.g., compliantly expand) causing a helical diameter of the first
balloon 5111 to increase, which can cause a portion (e.g., a curved
portion) of the first balloon 5111 to move closer to an inner surface of
a renal artery or a renal ostium.

Proximal Secondary Balloons

[0253] A primary balloon and a secondary balloon can be longitudinally
spaced apart along the length of a portion of a cryotherapeutic device
configured in accordance with several embodiments of the present
technology. For example, a secondary balloon can be part of an occlusion
member configured to fully or partially occlude a renal artery and/or a
renal ostium. FIGS. 52A-53 illustrate several embodiments of
cryotherapeutic devices that include proximal secondary balloons.

[0254] FIGS. 52A-52B illustrate a portion of a cryotherapeutic device 5200
including a cooling assembly 5202 and an occlusion member 5204
longitudinally spaced apart along an elongated shaft 5206 defining an
exhaust passage. The shaft 5206 can have a first stepped-down portion
5208, cooling-assembly exhaust portal 5209 at the first stepped-down
portion 5208, a second stepped-down portion 5210, and occlusion-member
exhaust portals 5211 at the second stepped-down portion 5210. The cooling
assembly 5202 and the occlusion member 5204 can be positioned at the
first stepped-down portion 5208 and the second stepped-down portion 5210,
respectively. The device 5200 can include a supply tube 5212, and the
cooling assembly 5202 can have orifice 5213 at the distal end of the
supply tube 5212. The cooling assembly 5202 also can include an
applicator 5214 with a first balloon 5215 that defines an expansion
chamber. The supply tube 5212 can angle out of the shaft 5206 and into
the first balloon 5215. The occlusion member 5204 can include a second
balloon 5216 defining an occlusion chamber. The second balloon 5216 can
be configured to passively receive refrigerant from the exhaust passage
through the occlusion-member exhaust portal 5211 and can be configured to
expand (e.g., compliantly expand) in response to back pressure from
refrigerant exhausted from the cooling assembly 5202. Both the cooling
assembly 5202 and the occlusion member 5204 can be at least partially
collapsible in a delivery state and are shown in FIGS. 52A-52B in an
expanded state and a deployed state, respectively. In the expanded state,
the occlusion member 5204 can have a cross-sectional dimension configured
to fully occlude a renal artery and/or a renal ostium.

[0255] As shown in FIG. 52B, the device 5200 can further include a first
elongated control member 5218, a second elongated control member 5220,
and a control tube 5222 with a first distal branch 5224 and a second
distal branch 5226. The shaft 5206 can further include a first distal
attachment point 5228, a second distal attachment point 5230, and a
flexing portion 5232 between the first stepped-down portion 5208 and the
second stepped-down portion 5210. The first elongated control member 5218
can extend along the control tube 5222, along the first distal branch
5224, and attach to the first distal attachment point 5228. The second
elongated control member 5220 can extend along the control tube 5222,
along the second distal branch 5226, and attach to the second distal
attachment point 5230. The device 5200 can be configured such that
increasing or decreasing tension of the first control member 5218 and/or
the second control member 5220 can control deflection of the shaft 5206.
The shaft 5206 can be flexible at the flexing portion 5232 to position
the first balloon against a vessel wall or ostium. In addition to or
instead of fully occluding the vessel or ostium, the occlusion member
5204 can be configured in the expanded state to support the shaft 5206
within a renal artery or a renal ostium to provide controlled
repositioning of the cooling assembly 5202 within the renal artery or the
renal ostium. For example, the cooling assembly 5202 can be repositioned
to cause therapeutically-effective, cryogenic renal-nerve modulation at
different portions of a renal artery or a renal ostium.

[0256]FIG. 53 illustrates a portion of a cryotherapeutic device 5300
similar to the cryotherapeutic device 5200 shown in FIGS. 53A-53B, but
the device 5300 has additional distal cooling and different supply and
control configurations. The device 5300 includes a cooling assembly 5302
and an occlusion member 5304 longitudinally spaced apart along an
elongated shaft 5306 defining an exhaust passage. The shaft 5306 can have
a distal attachment point 5307 and a distal tip portion 5308 defining a
distal expansion chamber. The cooling assembly 5302 includes an
applicator 5310 having a first balloon 5312 defining an expansion
chamber, and the occlusion member 5304 includes a second balloon 5314
defining an occlusion chamber fluidly separate from the exhaust passage.
The device 5300 further includes a filler tube 5316 extending to the
second balloon 5314 and a supply tube 5318 having a lateral branch 5320
extending to the first balloon 5312 and an angled distal portion 5322
extending to the distal tip portion 5308. The occlusion member 5304
further includes a filler orifice 5324 through which a filler material
can be supplied to the second balloon 5314. The cooling assembly 5302
further includes a first supply orifice 5326 configured to direct
refrigerant expansion into the first balloon 5312 and a second supply
orifice 5328 configured to direct refrigerant expansion into the distal
tip portion 5308.

[0257] The device 5300 further includes an elongated control member 5330
and a control tube 5332. The control member 5330 can extend along the
control tube 5332 and be attached to the distal attachment point 5307.
The device 5300 can be configured such that increasing or decreasing
tension of the control member 5330 can control deflection of the shaft
5306. In addition to or instead of fully occluding a vessel or ostium,
the occlusion member 5304 can be configured in the expanded state to
support the shaft 5306 within a renal artery or a renal ostium to provide
controlled repositioning of the cooling assembly 5302 within the renal
artery or the renal ostium. For example, the cooling assembly 5302 can be
repositioned to cause therapeutically-effective, cryogenic renal-nerve
modulation at different portions of a renal artery or a renal ostium.

Alternative Cooling

[0258] Cooling assemblies configured in accordance with several
embodiments of the present technology have a cooling mechanism in the
deployed state that does not involve evaporation of refrigerant. For
example, such embodiments can include cooling assemblies configured to
circulate liquid or supercritical refrigerant at cryogenic temperatures
to cause convective and conductive cooling through a primary
heat-transfer portion of an applicator. In such applicators, the flow
impedance of the supply can be generally equal to the flow impedance of
the exhaust. For example, the cross-sectional area of a supply lumen can
be generally equal to the cross-sectional area of an exhaust passage. In
some embodiments, cryotherapeutic devices having cooling assemblies
configured to circulate refrigerant without phase change can have
features to facilitate the supply of refrigerant to the cooling
assemblies and/or the exhaust of refrigerant from the cooling assemblies.
For example, a first pump can be included to increase the pressure of
refrigerant flowing to a cooling assembly and/or a vacuum source (e.g., a
second pump) can be included to decrease the pressure of refrigerant
flowing away from a cooling assembly. In addition to the first pump or
alternatively, refrigerant can be supplied from a pressurized source.
Based on operational considerations, e.g., refrigerant viscosity and flow
impedances of supply, exhaust, and heat-transfer portions of a
cryotherapeutic device, supply and exhaust pressures can be selected to
cause different flow rates of refrigerant. The flow rate can be selected,
for example, to correspond to a heat-transfer rate sufficient to cause
therapeutically-effective cryogenic renal nerve modulation.

[0259] FIG. 54 illustrates a portion of a cryotherapeutic device 5400 that
can be configured for convective heat transfer without refrigerant
phase-change. The device 5400 includes a cooling assembly 5402 at a
distal portion 5404 of an elongated shaft 5406 defining an exhaust
passage. The cooling assembly 5402 includes an applicator 5408 with a
balloon 5410 that defines a circulation chamber. The device 5400 also
includes a supply tube 5412 extending along the length of the shaft 5406
and into the balloon 5410, and the cooling assembly 5402 includes an
orifice 5414 at the distal end of the supply tube 5412. In several
embodiments, the supply tube 5412 is relatively large and configured to
transport liquid refrigerant, and the orifice 5414 is not configured to
cause a pressure drop sufficient to evaporate a refrigerant. When the
cooling assembly 5402 is in a deployed state, the balloon 5410 can be
configured to be filled with refrigerant in at least a substantially
liquid phase. The refrigerant can circulate from the supply tube 5412 to
the exhaust passage. FIG. 54 includes arrows 5416 indicating a direction
of refrigerant flow through the balloon 5410. The refrigerant can be a
liquid having a low freezing point (e.g., ethyl alcohol) and can be
transported through the supply tube 5412 at a cryogenic temperature.
Convective heat transfer between the refrigerant and the balloon 5410 can
cool a renal artery or a renal ostium to cause therapeutically-effective
renal nerve modulation.

[0260]FIG. 55 illustrates a portion of a cryotherapeutic device 5500 that
also can be configured for convective heat transfer without refrigerant
phase-change. The device 5500 includes a cooling assembly 5502 at a
distal portion 5504 of an elongated shaft 5506 including a shaft
partition 5508 dividing the shaft into a first longitudinal portion 5510
defining supply lumen and a second longitudinal portion 5512 defining an
exhaust passage. The cooling assembly 5502 includes an applicator 5514
with a balloon 5516 including a balloon partition 5518 that defines a
U-shaped chamber within the balloon 5516. The balloon 5516 can be
configured to circulate liquid refrigerant from the first longitudinal
portion 5510, through the U-shaped chamber, and into the second
longitudinal portion 5512. FIG. 55 includes an arrow 5520 indicating a
direction of refrigerant flow through the balloon 5516.

[0261] In several embodiments, a cooling assembly is configured to
circulate a supercritical fluid (e.g., supercritical nitrogen or water).
Supercritical fluids can provide significant cooling without phase
change, but typically must be maintained at relatively high pressures.
Cooling assemblies configured to circulate supercritical fluids can
include supply, heat-transfer, and exhaust structures having high
pressure ratings. For example, such cooling assemblies can include
non-expandable applicators (e.g., having metal walls). Such applicators
can be moveable during a treatment to contact different portions of a
renal artery or a renal ostium.

Additional Embodiments

[0262] Features of the cryotherapeutic-device components described above
and illustrated in FIGS. 1-5B and 12-55 can be modified to form
additional embodiments configured in accordance with the present
technology. For example, the cryotherapeutic device 1700 illustrated in
FIGS. 17A-17B and other cryotherapeutic devices described above and
illustrated in FIGS. 1-5B and 12-55 without guide members can include
guide members that extend near or through distal portions of balloons.
Similarly, the cryotherapeutic devices described above and illustrated in
FIGS. 1-5B and 12-55 can include control members configured to receive
control wires (e.g., pull wires). A control wire can be used, for
example, to control (e.g., deflect, angle, position, or steer) a cooling
assembly, an applicator, or another cryotherapeutic-device component from
outside the vasculature.

[0263] The cryotherapeutic-device components described above and
illustrated in FIGS. 1-5B and 12-55 include balloons having a variety of
features (e.g., shapes and compositions). In some cases, manufacturing
considerations and other factors can cause certain features to be more or
less desirable. For example, certain materials can be more compatible
with extrusion processes than with molding processes or vise versa.
Similarly, some balloon shapes can be more readily formed using certain
manufacturing processes than using other manufacturing processes. For
example, balloons having integral closed distal ends, in some cases, can
be difficult to form using extrusion. The balloons and balloon features
in the cryotherapeutic-device components described above and illustrated
in FIGS. 1-5B and 12-55 can be modified or interchanged according to such
factors. For example, distal necks (e.g., sealed distal necks) can be
substituted for integral closed distal ends in the balloons described
above and illustrated in FIGS. 1-5B and 12-55. This can be useful, for
example, to make the balloons more compatible with extrusion
manufacturing processes.

[0264] Features of the cryotherapeutic-device components described above
also can be interchanged to form additional embodiments of the present
technology. For example, the inner balloon 1514 of the cooling assembly
1502 illustrated in FIG. 15A can be incorporated into the cooling
assembly 1902 shown in FIGS. 19A-19C. As another example, the first
supply tube 1218 with the first angled distal portion 1222 of the
cryotherapeutic device 1200 illustrated in FIG. 12 can be incorporated
into the cooling assembly 1702 illustrated in FIGS. 17A-17B, with the
first angled distal portion 1222 configured to direct expansion of
refrigerant between the thermally-insulative members 1711.

[0265] Related Anatomy and Physiology

[0266] The Sympathetic Nervous System (SNS) is a branch of the autonomic
nervous system along with the enteric nervous system and parasympathetic
nervous system. It is always active at a basal level (called sympathetic
tone) and becomes more active during times of stress. Like other parts of
the nervous system, the sympathetic nervous system operates through a
series of interconnected neurons. Sympathetic neurons are frequently
considered part of the peripheral nervous system (PNS), although many lie
within the central nervous system (CNS). Sympathetic neurons of the
spinal cord (which is part of the CNS) communicate with peripheral
sympathetic neurons via a series of sympathetic ganglia. Within the
ganglia, spinal cord sympathetic neurons join peripheral sympathetic
neurons through synapses. Spinal cord sympathetic neurons are therefore
called presynaptic (or preganglionic) neurons, while peripheral
sympathetic neurons are called postsynaptic (or postganglionic) neurons.

[0267] At synapses within the sympathetic ganglia, preganglionic
sympathetic neurons release acetylcholine, a chemical messenger that
binds and activates nicotinic acetylcholine receptors on postganglionic
neurons. In response to this stimulus, postganglionic neurons principally
release noradrenaline (norepinephrine). Prolonged activation may elicit
the release of adrenaline from the adrenal medulla.

[0268] Once released, norepinephrine and epinephrine bind adrenergic
receptors on peripheral tissues. Binding to adrenergic receptors causes a
neuronal and hormonal response. The physiologic manifestations include
pupil dilation, increased heart rate, occasional vomiting, and increased
blood pressure. Increased sweating is also seen due to binding of
cholinergic receptors of the sweat glands.

[0269] The sympathetic nervous system is responsible for up- and
down-regulating many homeostatic mechanisms in living organisms. Fibers
from the SNS innervate tissues in almost every organ system, providing at
least some regulatory function to physiological features as diverse as
pupil diameter, gut motility, and urinary output. This response is also
known as sympatho-adrenal response of the body, as the preganglionic
sympathetic fibers that end in the adrenal medulla (but also all other
sympathetic fibers) secrete acetylcholine, which activates the secretion
of adrenaline (epinephrine) and to a lesser extent noradrenaline
(norepinephrine). Therefore, this response that acts primarily on the
cardiovascular system is mediated directly via impulses transmitted
through the sympathetic nervous system and indirectly via catecholamines
secreted from the adrenal medulla.

[0270] Science typically looks at the SNS as an automatic regulation
system, that is, one that operates without the intervention of conscious
thought. Some evolutionary theorists suggest that the sympathetic nervous
system operated in early organisms to maintain survival as the
sympathetic nervous system is responsible for priming the body for
action. One example of this priming is in the moments before waking, in
which sympathetic outflow spontaneously increases in preparation for
action.

[0271] 1. The Sympathetic Chain

[0272] As shown in FIG. 56, the SNS provides a network of nerves that
allows the brain to communicate with the body. Sympathetic nerves
originate inside the vertebral column, toward the middle of the spinal
cord in the intermediolateral cell column (or lateral horn), beginning at
the first thoracic segment of the spinal cord and are thought to extend
to the second or third lumbar segments. Because its cells begin in the
thoracic and lumbar regions of the spinal cord, the SNS is said to have a
thoracolumbar outflow. Axons of these nerves leave the spinal cord
through the anterior rootlet/root. They pass near the spinal (sensory)
ganglion, where they enter the anterior rami of the spinal nerves.
However, unlike somatic innervation, they quickly separate out through
white rami connectors which connect to either the paravertebral (which
lie near the vertebral column) or prevertebral (which lie near the aortic
bifurcation) ganglia extending alongside the spinal column.

[0273] In order to reach the target organs and glands, the axons should
travel long distances in the body, and, to accomplish this, many axons
relay their message to a second cell through synaptic transmission. The
ends of the axons link across a space, the synapse, to the dendrites of
the second cell. The first cell (the presynaptic cell) sends a
neurotransmitter across the synaptic cleft where it activates the second
cell (the postsynaptic cell). The message is then carried to the final
destination.

[0274] In the SNS and other components of the peripheral nervous system,
these synapses are made at sites called ganglia, discussed above. The
cell that sends its fiber is called a preganglionic cell, while the cell
whose fiber leaves the ganglion is called a postganglionic cell. As
mentioned previously, the preganglionic cells of the SNS are located
between the first thoracic (T1) segment and third lumbar (L3) segments of
the spinal cord. Postganglionic cells have their cell bodies in the
ganglia and send their axons to target organs or glands.

[0275] The ganglia include not just the sympathetic trunks but also the
cervical ganglia (superior, middle and inferior), which sends sympathetic
nerve fibers to the head and thorax organs, and the celiac and mesenteric
ganglia (which send sympathetic fibers to the gut).

[0276] 2. Innervation of the Kidneys

[0277] As FIG. 57 shows, the kidney is innervated by the renal plexus RP,
which is intimately associated with the renal artery. The renal plexus RP
is an autonomic plexus that surrounds the renal artery and is embedded
within the adventitia of the renal artery. The renal plexus RP extends
along the renal artery until it arrives at the substance of the kidney.
Fibers contributing to the renal plexus RP arise from the celiac
ganglion, the superior mesenteric ganglion, the aorticorenal ganglion and
the aortic plexus. The renal plexus RP, also referred to as the renal
nerve, is predominantly comprised of sympathetic components. There is no
(or at least very minimal) parasympathetic innervation of the kidney.

[0278] Preganglionic neuronal cell bodies are located in the
intermediolateral cell column of the spinal cord. Preganglionic axons
pass through the paravertebral ganglia (they do not synapse) to become
the lesser splanchnic nerve, the least splanchnic nerve, first lumbar
splanchnic nerve, second lumbar splanchnic nerve, and travel to the
celiac ganglion, the superior mesenteric ganglion, and the aorticorenal
ganglion. Postganglionic neuronal cell bodies exit the celiac ganglion,
the superior mesenteric ganglion, and the aorticorenal ganglion to the
renal plexus RP and are distributed to the renal vasculature.

[0279] 3. Renal Sympathetic Neural Activity

[0280] Messages travel through the SNS in a bidirectional flow. Efferent
messages may trigger changes in different parts of the body
simultaneously. For example, the sympathetic nervous system may
accelerate heart rate; widen bronchial passages; decrease motility
(movement) of the large intestine; constrict blood vessels; increase
peristalsis in the esophagus; cause pupil dilation, piloerection (goose
bumps) and perspiration (sweating); and raise blood pressure. Afferent
messages carry signals from various organs and sensory receptors in the
body to other organs and, particularly, the brain.

[0281] Hypertension, heart failure and chronic kidney disease are a few of
many disease states that result from chronic activation of the SNS,
especially the renal sympathetic nervous system. Chronic activation of
the SNS is a maladaptive response that drives the progression of these
disease states. Pharmaceutical management of the
renin-angiotensin-aldosterone system (RAAS) has been a longstanding, but
somewhat ineffective, approach for reducing over-activity of the SNS.

[0282] As mentioned above, the renal sympathetic nervous system has been
identified as a major contributor to the complex pathophysiology of
hypertension, states of volume overload (such as heart failure), and
progressive renal disease, both experimentally and in humans. Studies
employing radiotracer dilution methodology to measure overflow of
norepinephrine from the kidneys to plasma revealed increased renal
norepinephrine (NE) spillover rates in patients with essential
hypertension, particularly so in young hypertensive subjects, which in
concert with increased NE spillover from the heart, is consistent with
the hemodynamic profile typically seen in early hypertension and
characterized by an increased heart rate, cardiac output, and
renovascular resistance. It is now known that essential hypertension is
commonly neurogenic, often accompanied by pronounced sympathetic nervous
system overactivity.

[0283] Activation of cardiorenal sympathetic nerve activity is even more
pronounced in heart failure, as demonstrated by an exaggerated increase
of NE overflow from the heart and the kidneys to plasma in this patient
group. In line with this notion is the recent demonstration of a strong
negative predictive value of renal sympathetic activation on all-cause
mortality and heart transplantation in patients with congestive heart
failure, which is independent of overall sympathetic activity, glomerular
filtration rate, and left ventricular ejection fraction. These findings
support the notion that treatment regimens that are designed to reduce
renal sympathetic stimulation have the potential to improve survival in
patients with heart failure.

[0284] Both chronic and end stage renal disease are characterized by
heightened sympathetic nervous activation. In patients with end stage
renal disease, plasma levels of norepinephrine above the median have been
demonstrated to be predictive for both all-cause death and death from
cardiovascular disease. This is also true for patients suffering from
diabetic or contrast nephropathy. There is compelling evidence suggesting
that sensory afferent signals originating from the diseased kidneys are
major contributors to initiating and sustaining elevated central
sympathetic outflow in this patient group; this facilitates the
occurrence of the well known adverse consequences of chronic sympathetic
over activity, such as hypertension, left ventricular hypertrophy,
ventricular arrhythmias, sudden cardiac death, insulin resistance,
diabetes, and metabolic syndrome.

[0285] (i) Renal Sympathetic Efferent Activity

[0286] Sympathetic nerves to the kidneys terminate in the blood vessels,
the juxtaglomerular apparatus and the renal tubules. Stimulation of the
renal sympathetic nerves causes increased renin release, increased sodium
(Na+) reabsorption, and a reduction of renal blood flow. These components
of the neural regulation of renal function are considerably stimulated in
disease states characterized by heightened sympathetic tone and clearly
contribute to the rise in blood pressure in hypertensive patients. The
reduction of renal blood flow and glomerular filtration rate as a result
of renal sympathetic efferent stimulation is likely a cornerstone of the
loss of renal function in cardio-renal syndrome, which is renal
dysfunction as a progressive complication of chronic heart failure, with
a clinical course that typically fluctuates with the patient's clinical
status and treatment. Pharmacologic strategies to thwart the consequences
of renal efferent sympathetic stimulation include centrally acting
sympatholytic drugs, beta blockers (intended to reduce renin release),
angiotensin converting enzyme inhibitors and receptor blockers (intended
to block the action of angiotensin II and aldosterone activation
consequent to renin release) and diuretics (intended to counter the renal
sympathetic mediated sodium and water retention). However, the current
pharmacologic strategies have significant limitations including limited
efficacy, compliance issues, side effects and others.

[0287] (ii) Renal Sensory Afferent Nerve Activity

[0288] The kidneys communicate with integral structures in the central
nervous system via renal sensory afferent nerves. Several forms of "renal
injury" may induce activation of sensory afferent signals. For example,
renal ischemia, reduction in stroke volume or renal blood flow, or an
abundance of adenosine enzyme may trigger activation of afferent neural
communication. As shown in FIGS. 58A and 58B, this afferent communication
might be from the kidney to the brain or might be from one kidney to the
other kidney (via the central nervous system). These afferent signals are
centrally integrated and may result in increased sympathetic outflow.
This sympathetic drive is directed towards the kidneys, thereby
activating the RAAS and inducing increased renin secretion, sodium
retention, volume retention and vasoconstriction. Central sympathetic
over activity also impacts other organs and bodily structures innervated
by sympathetic nerves such as the heart and the peripheral vasculature,
resulting in the described adverse effects of sympathetic activation,
several aspects of which also contribute to the rise in blood pressure.

[0289] The physiology therefore suggests that (i) modulation of tissue
with efferent sympathetic nerves will reduce inappropriate renin release,
salt retention, and reduction of renal blood flow, and that (ii)
modulation of tissue with afferent sensory nerves will reduce the
systemic contribution to hypertension and other disease states associated
with increased central sympathetic tone through its direct effect on the
posterior hypothalamus as well as the contralateral kidney. In addition
to the central hypotensive effects of afferent renal denervation, a
desirable reduction of central sympathetic outflow to various other
sympathetically innervated organs such as the heart and the vasculature
is anticipated.

[0290] B. Additional Clinical Benefits of Renal Denervation

[0291] As provided above, renal denervation is likely to be valuable in
the treatment of several clinical conditions characterized by increased
overall and particularly renal sympathetic activity such as hypertension,
metabolic syndrome, insulin resistance, diabetes, left ventricular
hypertrophy, chronic end stage renal disease, inappropriate fluid
retention in heart failure, cardio-renal syndrome, and sudden death.
Since the reduction of afferent neural signals contributes to the
systemic reduction of sympathetic tone/drive, renal denervation might
also be useful in treating other conditions associated with systemic
sympathetic hyperactivity. Accordingly, renal denervation may also
benefit other organs and bodily structures innervated by sympathetic
nerves, including those identified in FIG. 56. For example, as previously
discussed, a reduction in central sympathetic drive may reduce the
insulin resistance that afflicts people with metabolic syndrome and Type
II diabetics. Additionally, patients with osteoporosis are also
sympathetically activated and might also benefit from the down regulation
of sympathetic drive that accompanies renal denervation.

[0292] C. Achieving Intravascular Access to the Renal Artery

[0293] In accordance with the present technology, neuromodulation of a
left and/or right renal plexus RP, which is intimately associated with a
left and/or right renal artery, may be achieved through intravascular
access. As FIG. 59A shows, blood moved by contractions of the heart is
conveyed from the left ventricle of the heart by the aorta. The aorta
descends through the thorax and branches into the left and right renal
arteries. Below the renal arteries, the aorta bifurcates at the left and
right iliac arteries. The left and right iliac arteries descend,
respectively, through the left and right legs and join the left and right
femoral arteries.

[0294] As FIG. 59B shows, the blood collects in veins and returns to the
heart, through the femoral veins into the iliac veins and into the
inferior vena cava. The inferior vena cava branches into the left and
right renal veins. Above the renal veins, the inferior vena cava ascends
to convey blood into the right atrium of the heart. From the right
atrium, the blood is pumped through the right ventricle into the lungs,
where it is oxygenated. From the lungs, the oxygenated blood is conveyed
into the left atrium. From the left atrium, the oxygenated blood is
conveyed by the left ventricle back to the aorta.

[0295] As will be described in greater detail later, the femoral artery
may be accessed and cannulated at the base of the femoral triangle just
inferior to the midpoint of the inguinal ligament. A catheter may be
inserted percutaneously into the femoral artery through this access site,
passed through the iliac artery and aorta, and placed into either the
left or right renal artery. This comprises an intravascular path that
offers minimally invasive access to a respective renal artery and/or
other renal blood vessels.

[0296] The wrist, upper arm, and shoulder region provide other locations
for introduction of catheters into the arterial system. For example,
catheterization of either the radial, brachial, or axillary artery may be
utilized in select cases. Catheters introduced via these access points
may be passed through the subclavian artery on the left side (or via the
subclavian and brachiocephalic arteries on the right side), through the
aortic arch, down the descending aorta and into the renal arteries using
standard angiographic technique.

[0297] D. Properties and Characteristics of the Renal Vasculature

[0298] Since neuromodulation of a left and/or right renal plexus RP may be
achieved in accordance with the present technology through intravascular
access, properties and characteristics of the renal vasculature may
impose constraints upon and/or inform the design of apparatus, systems,
and methods for achieving such renal neuromodulation. Some of these
properties and characteristics may vary across the patient population
and/or within a specific patient across time, as well as in response to
disease states, such as hypertension, chronic kidney disease, vascular
disease, end-stage renal disease, insulin resistance, diabetes, metabolic
syndrome, etc. These properties and characteristics, as explained herein,
may have bearing on the efficacy of the procedure and the specific design
of the intravascular device. Properties of interest may include, for
example, material/mechanical, spatial, fluid dynamic/hemodynamic and/or
thermodynamic properties.

[0299] As discussed previously, a catheter may be advanced percutaneously
into either the left or right renal artery via a minimally invasive
intravascular path. However, minimally invasive renal arterial access may
be challenging, for example, because as compared to some other arteries
that are routinely accessed using catheters, the renal arteries are often
extremely tortuous, may be of relatively small diameter, and/or may be of
relatively short length. Furthermore, renal arterial atherosclerosis is
common in many patients, particularly those with cardiovascular disease.
Renal arterial anatomy also may vary significantly from patient to
patient, which further complicates minimally invasive access. Significant
inter-patient variation may be seen, for example, in relative tortuosity,
diameter, length, and/or atherosclerotic plaque burden, as well as in the
take-off angle at which a renal artery branches from the aorta.
Apparatus, systems and methods for achieving renal neuromodulation via
intravascular access should account for these and other aspects of renal
arterial anatomy and its variation across the patient population when
minimally invasively accessing a renal artery.

[0300] In addition to complicating renal arterial access, specifics of the
renal anatomy also complicate establishment of stable contact between
neuromodulatory apparatus and a luminal surface or wall of a renal
artery. When the neuromodulatory apparatus includes a cryotherapeutic
device, consistent positioning, appropriate contact force applied by the
cryotherapeutic device to the vessel wall, and adhesion between the
cryo-applicator and the vessel wall are important for predictability.
However, navigation is impeded by the tight space within a renal artery,
as well as tortuosity of the artery. Furthermore, establishing consistent
contact is complicated by patient movement, respiration, and/or the
cardiac cycle because these factors may cause significant movement of the
renal artery relative to the aorta, and the cardiac cycle may transiently
distend the renal artery (i.e. cause the wall of the artery to pulse.

[0301] Even after accessing a renal artery and facilitating stable contact
between neuromodulatory apparatus and a luminal surface of the artery,
nerves in and around the adventia of the artery should be safely
modulated via the neuromodulatory apparatus. Effectively applying thermal
treatment from within a renal artery is non-trivial given the potential
clinical complications associated with such treatment. For example, the
intima and media of the renal artery are highly vulnerable to thermal
injury. As discussed in greater detail below, the intima-media thickness
separating the vessel lumen from its adventitia means that target renal
nerves may be multiple millimeters distant from the luminal surface of
the artery. Sufficient energy should be delivered to or heat removed from
the target renal nerves to modulate the target renal nerves without
excessively cooling or heating the vessel wall to the extent that the
wall is frozen, desiccated, or otherwise potentially affected to an
undesirable extent. A potential clinical complication associated with
excessive heating is thrombus formation from coagulating blood flowing
through the artery. Given that this thrombus may cause a kidney infarct,
thereby causing irreversible damage to the kidney, thermal treatment from
within the renal artery should be applied carefully. Accordingly, the
complex fluid mechanics and thermodynamic conditions present in the renal
artery during treatment, particularly those that may impact heat transfer
dynamics at the treatment site, may be important in applying energy
(e.g., heating thermal energy) and/or removing heat from the tissue
(e.g., cooling thermal conditions) from within the renal artery.

[0302] The neuromodulatory apparatus should also be configured to allow
for adjustable positioning and repositioning of the energy delivery
element within the renal artery since location of treatment may also
impact clinical efficacy. For example, it may be tempting to apply a full
circumferential treatment from within the renal artery given that the
renal nerves may be spaced circumferentially around a renal artery. In
some situations, full-circle lesion likely resulting from a continuous
circumferential treatment may be potentially related to renal artery
stenosis. Therefore, the formation of more complex lesions along a
longitudinal dimension of the renal artery via the cryotherapeutic
devices and/or repositioning of the neuromodulatory apparatus to multiple
treatment locations may be desirable. It should be noted, however, that a
benefit of creating a circumferential ablation may outweigh the potential
of renal artery stenosis or the risk may be mitigated with certain
embodiments or in certain patients and creating a circumferential
ablation could be a goal. Additionally, variable positioning and
repositioning of the neuromodulatory apparatus may prove to be useful in
circumstances where the renal artery is particularly tortuous or where
there are proximal branch vessels off the renal artery main vessel,
making treatment in certain locations challenging. Manipulation of a
device in a renal artery should also consider mechanical injury imposed
by the device on the renal artery. Motion of a device in an artery, for
example by inserting, manipulating, negotiating bends and so forth, may
contribute to dissection, perforation, denuding intima, or disrupting the
interior elastic lamina.

[0303] Blood flow through a renal artery may be temporarily occluded for a
short time with minimal or no complications. However, occlusion for a
significant amount of time should be avoided because to prevent injury to
the kidney such as ischemia. It could be beneficial to avoid occlusion
all together or, if occlusion is beneficial to the embodiment, to limit
the duration of occlusion, for example to 2-5 minutes.

[0304] Based on the above described challenges of (1) renal artery
intervention, (2) consistent and stable placement of the treatment
element against the vessel wall, (3) effective application of treatment
across the vessel wall, (4) positioning and potentially repositioning the
treatment apparatus to allow for multiple treatment locations, and (5)
avoiding or limiting duration of blood flow occlusion, various
independent and dependent properties of the renal vasculature that may be
of interest include, for example, (a) vessel diameter, vessel length,
intima-media thickness, coefficient of friction, and tortuosity; (b)
distensibility, stiffness and modulus of elasticity of the vessel wall;
(c) peak systolic, end-diastolic blood flow velocity, as well as the mean
systolic-diastolic peak blood flow velocity, and mean/max volumetric
blood flow rate; (d) specific heat capacity of blood and/or of the vessel
wall, thermal conductivity of blood and/or of the vessel wall, and/or
thermal convectivity of blood flow past a vessel wall treatment site
and/or radiative heat transfer; (e) renal artery motion relative to the
aorta induced by respiration, patient movement, and/or blood flow
pulsatility: and (f) as well as the take-off angle of a renal artery
relative to the aorta. These properties will be discussed in greater
detail with respect to the renal arteries. However, dependent on the
apparatus, systems and methods utilized to achieve renal neuromodulation,
such properties of the renal arteries, also may guide and/or constrain
design characteristics.

[0305] As noted above, an apparatus positioned within a renal artery
should conform to the geometry of the artery. Renal artery vessel
diameter, DRA, typically is in a range of about 2-10 mm, with most
of the patient population having a DRA of about 4 mm to about 8 mm
and an average of about 6 mm. Renal artery vessel length, LRA,
between its ostium at the aorta/renal artery juncture and its distal
branchings, generally is in a range of about 5-70 mm, and a significant
portion of the patient population is in a range of about 20-50 mm. Since
the target renal plexus is embedded within the adventitia of the renal
artery, the composite Intima-Media Thickness, IMT, (i.e., the radial
outward distance from the artery's luminal surface to the adventitia
containing target neural structures) also is notable and generally is in
a range of about 0.5-2.5 mm, with an average of about 1.5 mm. Although a
certain depth of treatment is important to reach the target neural
fibers, the treatment should not be too deep (e.g., >5 mm from inner
wall of the renal artery) to avoid non-target tissue and anatomical
structures such as the renal vein.

[0306] An additional property of the renal artery that may be of interest
is the degree of renal motion relative to the aorta induced by
respiration and/or blood flow pulsatility. A patient's kidney, which is
located at the distal end of the renal artery, may move as much as 4''
cranially with respiratory excursion. This may impart significant motion
to the renal artery connecting the aorta and the kidney, thereby
requiring from the neuromodulatory apparatus a unique balance of
stiffness and flexibility to maintain contact between the cryo applicator
or other thermal treatment element and the vessel wall during cycles of
respiration. Furthermore, the take-off angle between the renal artery and
the aorta may vary significantly between patients, and also may vary
dynamically within a patient, e.g., due to kidney motion. The take-off
angle generally may be in a range of about 30°-135°.

[0307] The foregoing embodiments of cryotherapeutic devices are configured
to accurately position the cryo applicators in and/or near the renal
artery and/or renal ostium via a femoral approach, transradial approach,
or another suitable vascular approach. In any of the foregoing
embodiments described above with reference to FIGS. 1-55, single balloons
can be configured to be inflated to diameters of about 3 mm to about 8
mm, and multiple-balloons can collectively be configured to be inflated
to diameters of about 3 mm to about 8 mm, and in several embodiments 4 mm
to 8 mm. Additionally, in any of the embodiments shown and described
above with reference to FIGS. 1-55, the balloons can individually and/or
collectively have a length of about 8 mm to about 15 mm, and in several
embodiments 10 mm. For example, several specific embodiments of the
devices shown in FIGS. 1-55 can have a 10 mm long balloon that is
configured to be inflated to a diameter of 4 mm to 8 mm. The shaft of the
devices described above with reference to any of the embodiments shown in
FIGS. 1-55 can be sized to fit within a 6 Fr sheath, such as a 4 Fr shaft
size.

CONCLUSION

[0308] The above detailed descriptions of embodiments of the technology
are not intended to be exhaustive or to limit the technology to the
precise form disclosed above. Although specific embodiments of, and
examples for, the technology are described above for illustrative
purposes, various equivalent modifications are possible within the scope
of the technology, as those skilled in the relevant art will recognize.
For example, while steps are presented in a given order, alternative
embodiments may perform steps in a different order. The various
embodiments described herein may also be combined to provide further
embodiments.

[0309] From the foregoing, it will be appreciated that specific
embodiments of the technology have been described herein for purposes of
illustration, but well-known structures and functions have not been shown
or described in detail to avoid unnecessarily obscuring the description
of the embodiments of the technology. Where the context permits, singular
or plural terms may also include the plural or singular term,
respectively.

[0310] Moreover, unless the word "or" is expressly limited to mean only a
single item exclusive from the other items in reference to a list of two
or more items, then the use of "or" in such a list is to be interpreted
as including (a) any single item in the list, (b) all of the items in the
list, or (c) any combination of the items in the list. Additionally, the
term "comprising" is used throughout to mean including at least the
recited feature(s) such that any greater number of the same feature
and/or additional types of other features are not precluded. It will also
be appreciated that specific embodiments have been described herein for
purposes of illustration, but that various modifications may be made
without deviating from the technology. Further, while advantages
associated with certain embodiments of the technology have been described
in the context of those embodiments, other embodiments may also exhibit
such advantages, and not all embodiments need necessarily exhibit such
advantages to fall within the scope of the technology. Accordingly, the
disclosure and associated technology can encompass other embodiments not
expressly shown or described herein.